Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Robert V. Considine, Ph.D., Madhur K. Sinha, Ph.D., Mark L. Heiman, Ph.D., Aidas Kriauciunas, Ph.D., Thomas W. Stephens, Ph.D., Mark R. Nyce, M.S., Joanna P. Ohannesian, B.S.N., Cheryl C. Marco, R.D., Linda J. McKee, M.H.S., Thomas L. Bauer, M.D., and José F. Caro, M.D.
Background Leptin, the product of the ob gene, is a hormonesecreted by adipocytes. Animals with mutations in the ob geneare obese and lose weight when given leptin, but little is knownabout the physiologic actions of leptin in humans.
Methods Using a newly developed radioimmunoassay, we measuredserum concentrations of leptin in 136 normal-weight subjectsand 139 obese subjects (body-mass index, >27.3 for men and>27.8 for women; the body-mass index was defined as the weightin kilograms divided by the square of the height in meters).The measurements were repeated in seven obese subjects afterweight loss and during maintenance of the lower weight. Theob messenger RNA (mRNA) content of adipocytes was determinedin 27 normal-weight and 27 obese subjects.
Results The mean (±SD) serum leptin concentrations were31.3±24.1 ng per milliliter in the obese subjects and7.5±9.3 ng per milliliter in the normal-weight subjects(P<0.001). There was a strong positive correlation betweenserum leptin concentrations and the percentage of body fat (r= 0.85, P<0.001). The ob mRNA content of adipocytes was abouttwice as high in the obese subjects as in the normal-weightsubjects (P = 0.005) and was correlated with the percentageof body fat (r = 0.68, P<0.001) in the 54 subjects in whomit was measured. In the seven obese subjects studied after weightloss, both serum leptin concentrations and ob mRNA content ofadipocytes declined, but these measures increased again duringthe maintenance of the lower weight.
Conclusions Serum leptin concentrations are correlated withthe percentage of body fat, suggesting that most obese personsare insensitive to endogenous leptin production.
The ob gene is an adipocyte-specific gene that encodes leptin,a protein that regulates body weight.1 In mice, mutations inthe ob gene that result in a lack of circulating leptin causeobesity. The administration of recombinant leptin causes weightloss in these mice.2,3,4
We have reported the complete coding sequence of human ob complementaryDNA (cDNA),5 a finding recently confirmed by others.6 We didnot detect any mutations in the gene in five obese subjects.In eight normal-weight and eight obese subjects the amount ofob messenger RNA (mRNA) in adipocytes was correlated with bodyweight. An increase in expression of the ob gene in obese subjectshas since been reported by other investigators.7,8 These resultssuggest that the ob gene encodes a protein that informs thebrain of the amount of adipose tissue present in the body.
In this study we investigated whether leptin can be detectedin serum at concentrations that correlate with body weight andwhether serum leptin concentrations are reduced by weight loss.
Methods
Subjects
We studied 136 lean subjects (84 women and 52 men; mean [±SD]age, 29±7 years) and 139 obese subjects (99 women and40 men; mean age, 37±11 years). The mean body-mass index(BMI), defined as the weight in kilograms divided by the squareof the height in meters, was 23.0±2.5 for the normal-weightsubjects and 35.1±7.2 for the obese subjects. Obesitywas defined as a BMI >27.3 for men and >27.8 for women,which is approximately 120 percent of ideal body weight.9 Noneof the subjects were taking any medication or had any evidenceof metabolic disease other than obesity, and all reported thattheir body weight had been stable for at least three monthsbefore the study. A blood sample was collected from each subjectwhile fasting, and the serum was frozen at -80°C until analysis.
We performed biopsies of abdominal subcutaneous adipose tissue10in 27 of the lean subjects (15 women and 12 men) and 27 of theobese subjects (17 women and 10 men). The tissue samples weretransported in saline to the laboratory, where they were immediatelydigested with collagenase and the cells isolated.10
To study the effect of weight loss, seven of the obese subjects(six women and one man; BMI, 40.4±5.2; age, 37±13years) were fed a liquid-protein diet providing 800 kcal perday (Optifast 800, Sandoz Nutrition, Minneapolis). In additionto the base-line studies described above, blood was drawn andbiopsies performed when the subjects had reduced their bodyweight by 10 percent and again after they had maintained thelower body weight for four weeks.
The effect of food consumption on serum leptin concentrationswas studied in a separate group of four normal-weight subjects(two women and two men; BMI, 24.3±2.6; age, 40±8years) and three obese women (BMI, 32.2±2.7; age, 43±4years). After an overnight fast, blood samples were drawn every60 minutes for 8 hours. Breakfast (total energy, 848 kcal: protein,14 percent; carbohydrate, 52 percent; and fat, 34 percent) wasgiven after the fasting sample was collected, and lunch (totalenergy, 902 kcal; protein, 13 percent; carbohydrate, 52 percent;and fat, 35 percent) was given four hours later.
All protocols were approved by the institutional review boardat Thomas Jefferson University, and all the subjects gave informedconsent.
Radioimmunoassay for Serum Leptin
Antihuman leptin antiserum was raised in rabbits immunized withrecombinant leptin.11 This antiserum did not cross-react withinsulin, insulin-like growth factor 1, or glucagon in dosesof 10 µg per milliliter. The leptin was radiolabeled withiodine 125 by the Bolton–Hunter method12 and purifiedby gel filtration using Sephadex G-25 (Pharmacia Biotech, Piscataway,N.J.). The specific activity was about 30 µCi per microgram.Unlabeled and 125I-labeled leptin was stable for at least 30days at 4°C.11
In the leptin radioimmunoassay, recombinant leptin in charcoal-treatedserum or 200 µl of test serum (in duplicate) was incubatedin phosphate-buffered saline (pH 7.4) containing 0.1 percentTriton X-100 with antileptin serum (at a dilution of 1:2000)for 16 hours at 4°C in a total volume of 400 µl. 125I-labeledleptin (about 30,000 counts per minute in 100 µl) wasthen added, and the incubation continued for an additional 24hours. Antiserum-bound 125I-labeled leptin was precipitatedby the addition of 100 µl of sheep antirabbit IgG serum(Antibodies Inc., Davis, Calif.), 100 µl of normal rabbitserum (GIBCO BRL, Gaithersburg, Md.), and 100 µl of 10percent polyethylene glycol. The tubes were centrifuged for15 minutes at 2200 revolutions per minute, after which the supernatantwas decanted and the pellet counted in a Packard 5000 gammacounter (Packard, Downers Grove, Ill.). In the absence of unlabeledleptin, the antiserum dilution used precipitated 12±1percent of the 125I-labeled leptin added; 1.4±0.1 percentwas precipitated in the absence of antiserum. The limit of detectionwas 0.4 ng per milliliter, the intraassay standard coefficientof variation was 11.6 percent, and the interassay coefficientof variation was 20.8 percent. Serum values that were undetectablewere assigned a value of 0.4 ng per milliliter for purposesof analysis.
Reverse-Transcriptase Polymerase Chain Reaction
Total adipocyte RNA was obtained by guanidinium thiocyanate–phenol–chloroformextraction.13 A reverse-transcriptase polymerase chain reaction14was performed with a thermocycler (model 9600, Perkin-Elmer,Foster City, Calif.) with a final primer concentration of 10pmol per 100-µl reaction, as described previously.5 Thedata are expressed as the ratio of ob cDNA to actin cDNA. Therewas no difference in the amount of actin cDNA among the subjectsstudied.
Other Analyses
Serum insulin was measured by radioimmunoassay (Linco Research,St. Charles, Mo.). Serum glucose was measured by the glucoseoxidase method with a glucose analyzer 2 (Beckman, Brea, Calif.).The percentage of body fat was determined for 108 normal-weightand 71 obese subjects by bioelectric impedance analysis (RJLSystems, Mt. Clemens, Mich.).
Statistical Analysis
The results in the normal-weight and obese subjects were comparedby means of t-tests. Because of extreme values in the distributionsof serum leptin concentrations and percentages of body fat,the relations between continuous variables were evaluated bySpearman correlations. The Wilcoxon rank-sum test was used toevaluate differences in serum leptin concentrations and othermeasures according to sex and race. Three regression modelswere fitted to determine the relation between the serum leptinconcentration and the percentage of body fat. The models includeda simple linear relation of the percentage of body fat withthe log of the serum leptin concentration, the log of the percentageof body fat with the log of the serum leptin concentration,and a quadratic model (percentage of body fat and the squareof the percentage of body fat). A similar set of regressionmodels was developed for the relation between expression ofthe ob gene and the percentage of body fat. Finally, multipleregression analysis with use of the quadratic model was performedto evaluate the relation of other variables to the serum leptinconcentration, after control for the percentage of body fat.All analyses were two-tailed and conducted with SAS software(version 6.10 for Windows; SAS Institute, Cary, N.C.). No adjustmentswere made for multiple testing.
Results
The mean serum leptin concentration in the 139 obese subjectswas 31.3±24.1 ng per milliliter, as compared with 7.5±9.3ng per milliliter in the normal-weight subjects (P<0.001).Seven percent of the latter group but none of the former hadundetectable serum leptin concentrations. The lowest serum leptinconcentration detected in an obese subject was 1.7 ng per milliliter.Body-composition analysis was performed in 108 of the normal-weightsubjects (64 women and 44 men) and 71 of the obese subjects(47 women and 24 men). There was a strong positive correlation(r = 0.85, P<0.001) between the serum leptin concentrationand the percentage of body fat (Figure 1). Serum leptin concentrationswere also correlated with the BMI (r = 0.66, P<0.001), fastingserum insulin concentration (r = 0.57, P<0.001), and age(r = 0.26, P<0.001). Serum leptin concentrations were significantlyhigher in normal-weight women than in normal-weight men andin obese women than in obese men when the groups were definedby BMI. However, when women and men with equivalent percentagesof body fat were compared, there was no difference between thesexes.
Figure 1. The Relation between the Percentage of Body Fat and the Serum Leptin Concentration in 136 Normal-Weight and 139 Obese Subjects.
The inset shows the natural log of the serum leptin concentration plotted against the percentage of body fat.
A regression model to evaluate the relation between the serumleptin concentration and the percentage of body fat was developed.Of the models tested, the quadratic model (r2 = 0.72) providedthe best fit. There was no improvement in the fit of the modelwith the addition of the BMI, age, fasting serum insulin orglucose concentration, sex, or race. These factors thereforehad no independent effect on the serum leptin concentrationafter we controlled for the percentage of body fat.
Ob mRNA in abdominal subcutaneous adipocytes was measured in54 subjects. The ob mRNA content in the 27 obese subjects wasabout twice as high as in the 27 normal-weight subjects (29.0±8.7vs. 18.8±10.9 relative units, P = 0.005). Like the serumleptin concentration, the ob mRNA content of the adipocyteswas correlated with the percentage of body fat (r = 0.68, P<0.001)(Figure 2), BMI (r = 0.70, P<0.001), and age (r = 0.38, P= 0.01). However, after we controlled for the percentage ofbody fat there was no independent effect of BMI, age, or sexin the analysis with the quadratic model.
Figure 2. Correlation between Expression of the ob Gene in Adipocytes and the Percentage of Body Fat in 27 Normal-Weight and 27 Obese Subjects.
The data are expressed as the ratio of ob cDNA to actin cDNA. There was no difference in the amount of actin cDNA among the subjects studied.
Among the seven obese subjects who were fed 800 kcal daily,four lost 10 percent of their initial weight in 8 weeks andthree in 12 weeks (Figure 3). After weight reduction, thesesubjects' fasting serum insulin concentrations decreased significantly,but their fasting serum glucose concentrations did not changemarkedly (Table 1). The mean serum leptin concentration decreasedby 53 percent and the ob mRNA content of adipocytes decreasedby 38 percent during the same period (Figure 3). During thesubsequent four-week period of weight maintenance, the meanserum leptin concentration increased again slightly and theob mRNA content rose, but not to values significantly differentfrom those before weight loss.
Figure 3. Effect of Weight Loss on Serum Leptin Concentrations and Expression of the ob Gene in Seven Obese Subjects, Expressed as a Percentage of the Initial Value.
A 10 percent reduction in body weight was achieved in seven obese subjects. The reduced body weight was then maintained for four weeks. The values shown are means ±SD. The initial values were as follows: serum leptin, 50.2±9.8 ng per milliliter; ob mRNA, 44.6±9.4 relative units; and weight, 111.4±13.9 kg. The asterisk denotes P = 0.05 for the comparison with the initial value.
Table 1. Body-Mass Index and Fasting Serum Biochemical Values in Seven Obese Subjects before and after Weight Loss.
Serum leptin concentrations did not change significantly inthe seven subjects studied before and after two meals. Seruminsulin and glucose concentrations increased transiently aftereach of the meals.
Discussion
We found that leptin, the protein product of the ob gene, isdetectable in serum and that obese subjects have higher serumleptin concentrations than normal-weight subjects. Althoughseveral factors may contribute to the elevation of serum leptinconcentrations in obesity, the values were most closely correlatedwith the percentage of body fat. The accuracy of body-fat determinationby bioelectric impedance analysis is limited,15 but the strengthof the correlation (r = 0.85, P<0.001) is much greater thanthat for any other variable tested. It therefore appears that,in humans, serum leptin concentrations reflect the amount ofadipose tissue in the body.
The mechanism by which the increase in body fat is translatedinto an increase in serum leptin appears to involve inductionof the ob gene. We found a significantly greater amount of obmRNA in adipocytes from obese subjects than in those from normal-weightsubjects. The fact that in obese subjects serum leptin increasessignificantly more (to four times the initial value) than doesob mRNA (to twice the initial value) suggests that hypertrophyof adipocytes leads to an increase in leptin production by individualcells, to approximately twice the initial value. Recent studiesin humans7,8 and rodents16,17,18 support the concept that serumleptin concentrations are regulated by direct changes in theexpression of the ob gene. It appears therefore that changesin body fat are translated into changes in serum leptin at thelevel of ob gene expression.
We found that a reduction of 10 percent in body weight was associatedwith a reduction of 53 percent in serum leptin, but that serumleptin concentrations increased slightly during the maintenanceperiod, during which body weight did not change. The large fluctuationsin serum leptin concentrations in the presence of relativelysmall changes in body weight suggest that leptin secretion isregulated by other factors in addition to the size of the adipose-tissuedepot. One of these factors may be caloric intake. While eating800 kcal a day, the subjects were in negative caloric balance,which could be a signal to the body to reduce leptin productionso that appetite would not be inhibited. During the maintenanceperiod, food intake was increased to maintain the lower bodyweight. Energy expenditure probably also decreased during themaintenance period,19 aiding in the restoration of caloric balanceand thus allowing serum leptin concentrations to increase again.
Several potential signals could mediate the reduction in serumleptin concentrations in response to caloric restriction. Fastingserum insulin concentrations decreased during weight loss, butthe postprandial rise in serum insulin during the period offrequent sampling was not associated with any change in serumleptin concentrations. The feeding experiment does not ruleout the possibility that long-term changes in insulin secretionalter serum leptin concentrations.
The significant correlation between the serum leptin concentrationand the percentage of body fat suggests that adipocytes aresignaling the brain about the size of the adipose-tissue depot.If the action of leptin in humans is similar to that in rodents,2,3,4appetite should decrease and energy expenditure should increase,which together should result in weight loss. The finding ofincreased serum leptin concentrations in obese subjects suggestsdecreased sensitivity to leptin, although the detection of leptinby immunologic methods does not prove that it is biologicallyactive. No functional and structural abnormalities of the leptin-effectorsystem in humans are currently known. However, diet-inducedobesity in normal mice is an example of decreased sensitivityto leptin, because larger doses of leptin were required to induceweight loss in these mice than in leptin-deficient mice.4 Thedb/db mouse provides an example of unresponsiveness to leptin.3,4
In summary, leptin, the protein product of the ob gene, is detectablein serum; its concentration is correlated with the percentageof body fat and is elevated in obese subjects. These resultssuggest that obesity in humans is more likely to be due to centralmechanisms regulating food intake and energy expenditure thanto defective signaling by adipocytes to these central mechanisms.
Supported in part by a grant (R01 DK45592) from the NationalInstitutes of Health and a grant from the Margaret Q. LandenbergerFoundation.
We are indebted to Ms. Irina Opentanova and Mr. Stuart Triesterfor their excellent technical assistance and to Dr. RichardDiMarchi for intellectual encouragement.
Source Information
From the Divisions of Endocrinology and Metabolism (R.V.C., M.K.S., M.R.N., J.P.O., C.C.M., J.F.C.) and Clinical Pharmacology, Biostatistics Section (L.J.M.), Department of Medicine, and the Department of Surgery (T.L.B.), Jefferson Medical College of Thomas Jefferson University, Philadelphia; and Eli Lilly Research Laboratories, Indianapolis (M.L.H., A.K., T.W.S.).
Address reprint requests to Dr. Considine at Thomas Jefferson University, 1025 Walnut St., 813 College Bldg., Philadelphia, PA 19107.
References
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432. [Erratum, Nature 1995;374:479.] [CrossRef][Medline]
Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540-543. [Free Full Text]
Halaas JL, Gajiwala KS, Maffei M, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-546. [Free Full Text]
Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269:546-549. [Free Full Text]
Considine RV, Considine EL, Williams CJ, et al. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest 1995;95:2986-2988.
Masuzaki H, Ogawa Y, Isse N, et al. Human obese gene expression: adipocyte-specific expression and regional differences in the adipose tissue. Diabetes 1995;44:855-858. [Abstract]
Lönnqvist F, Arner P, Nordfors L, Schalling M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med 1995;1:950-953. [CrossRef][Medline]
Hamilton BS, Paglia D, Kwan AYM, Deitel M. Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med 1995;1:953-956. [CrossRef][Medline]
NIH Technology Assessment Conference Panel. Methods for voluntary weight loss and control. Ann Intern Med 1992;116:942-949.
Kolaczynski JW, Morales LM, Moore JH Jr, et al. A new technique for biopsy of human abdominal fat under local anaesthesia with lidocaine. Int J Obes Relat Metab Disord 1994;18:161-166. [Medline]
Stephens TW, Basinski M, Bristow PK, et al. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 1995;377:530-532. [CrossRef][Medline]
Bolton AE, Hunter WM. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J 1973;133:529-539. [Medline]
Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156-159. [Medline]
Saiki RK, Scharf S, Faloona F, et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985;230:1350-1354. [Free Full Text]
Jebb SA, Elia M. Techniques for the measurement of body composition: a practical guide. Int J Obes Relat Metab Disord 1993;17:611-621. [Medline]
De Vos P, Saladin R, Auwerx J, Staels B. Induction of ob gene expression by corticosteroids is accompanied by body weight loss and reduced food intake. J Biol Chem 1995;270:15958-15961. [Free Full Text]
Funahashi T, Shimomura I, Hiraoka H, et al. Enhanced expression of rat obese (ob) gene in adipose tissues of ventromedial hypothalamus (VMH)-lesioned rats. Biochem Biophys Res Commun 1995;211:469-475. [CrossRef][Medline]
Murakami T, Shima K. Cloning of rat obese cDNA and its expression in obese rats. Biochem Biophys Res Commun 1995;209:944-952. [CrossRef][Medline]
Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med 1995;332:621-628. [Free Full Text]
Venner, A. A, Doyle-Baker, P. K, Lyon, M. E, Fung, T. S
(2009). A meta-analysis of leptin reference ranges in the healthy paediatric prepubertal population. Ann Clin Biochem
46: 65-72
[Abstract][Full Text]
Hajer, G. R., van Haeften, T. W., Visseren, F. L.J.
(2008). Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J
29: 2959-2971
[Abstract][Full Text]
Shan, J., Nguyen, T. B., Totary-Jain, H., Dansky, H., Marx, S. O., Marks, A. R.
(2008). Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors. Proc. Natl. Acad. Sci. USA
105: 19006-19011
[Abstract][Full Text]
Zhang, R., Dhillon, H., Yin, H., Yoshimura, A., Lowell, B. B., Maratos-Flier, E., Flier, J. S.
(2008). Selective Inactivation of Socs3 in SF1 Neurons Improves Glucose Homeostasis without Affecting Body Weight. Endocrinology
149: 5654-5661
[Abstract][Full Text]
Vasselli, J. R.
(2008). Fructose-induced leptin resistance: discovery of an unsuspected form of the phenomenon and its significance. Focus on "Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding," by Shapiro et al.. Am. J. Physiol. Regul. Integr. Comp. Physiol.
295: R1365-R1369
[Full Text]
Martin, S. S., Qasim, A., Reilly, M. P.
(2008). Leptin Resistance: A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease. J Am Coll Cardiol
52: 1201-1210
[Abstract][Full Text]
Nair, P., Radford, K., Fanat, A., Janssen, L. J., Peters-Golden, M., Cox, P. G.
(2008). The Effects of Leptin on Airway Smooth Muscle Responses. Am. J. Respir. Cell Mol. Bio.
39: 475-481
[Abstract][Full Text]
Trotter-Mayo, R. N., Roberts, M. R.
(2008). Leptin Acts in the Periphery to Protect Thymocytes from Glucocorticoid-Mediated Apoptosis in the Absence of Weight Loss. Endocrinology
149: 5209-5218
[Abstract][Full Text]
Korda, M., Kubant, R., Patton, S., Malinski, T.
(2008). Leptin-induced endothelial dysfunction in obesity. Am. J. Physiol. Heart Circ. Physiol.
295: H1514-H1521
[Abstract][Full Text]
Alexander, B. T., Ojeda, N. B.
(2008). Slow Prenatal Growth and Accelerated Postnatal Growth: Critical Influences on Adult Blood Pressure. Hypertension
52: 613-614
[Full Text]
White, U. A., Stewart, W. C., Mynatt, R. L., Stephens, J. M.
(2008). Neuropoietin Attenuates Adipogenesis and Induces Insulin Resistance in Adipocytes. J. Biol. Chem.
283: 22505-22512
[Abstract][Full Text]
Geiger, B. M., Behr, G. G., Frank, L. E., Caldera-Siu, A. D., Beinfeld, M. C., Kokkotou, E. G., Pothos, E. N.
(2008). Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats. FASEB J.
22: 2740-2746
[Abstract][Full Text]
Bloomgarden, Z. T.
(2008). Approaches to Treatment of Pre-Diabetes and Obesity and Promising New Approaches to Type 2 Diabetes. Diabetes Care
31: 1461-1466
[Full Text]
Villareal, D. T., Shah, K., Banks, M. R., Sinacore, D. R., Klein, S.
(2008). Effect of Weight Loss and Exercise Therapy on Bone Metabolism and Mass in Obese Older Adults: A One-Year Randomized Controlled Trial. J. Clin. Endocrinol. Metab.
93: 2181-2187
[Abstract][Full Text]
Roper, J., Francois, F., Shue, P. L., Mourad, M. S., Pei, Z., Olivares de Perez, A. Z., Perez-Perez, G. I., Tseng, C.-H., Blaser, M. J.
(2008). Leptin and Ghrelin in Relation to Helicobacter pylori Status in Adult Males. J. Clin. Endocrinol. Metab.
93: 2350-2357
[Abstract][Full Text]
Mori, M. A., Araujo, R. C., Reis, F. C.G., Sgai, D. G., Fonseca, R. G., Barros, C. C., Merino, V. F., Passadore, M., Barbosa, A. M., Ferrari, B., Carayon, P., Castro, C. H.M., Shimuta, S. I., Luz, J., Bascands, J.-L., Schanstra, J. P., Even, P. C., Oliveira, S. M., Bader, M., Pesquero, J. B.
(2008). Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity. Diabetes
57: 1491-1500
[Abstract][Full Text]
Volpe, S. L., Kobusingye, H., Bailur, S., Stanek, E.
(2008). Effect of Diet and Exercise on Body Composition, Energy Intake and Leptin Levels in Overweight Women and Men. J. Am. Coll. Nutr.
27: 195-208
[Abstract][Full Text]
Vickers, M. H., Gluckman, P. D., Coveny, A. H., Hofman, P. L., Cutfield, W. S., Gertler, A., Breier, B. H., Harris, M.
(2008). The Effect of Neonatal Leptin Treatment on Postnatal Weight Gain in Male Rats Is Dependent on Maternal Nutritional Status during Pregnancy. Endocrinology
149: 1906-1913
[Abstract][Full Text]
Metlakunta, A. S., Sahu, M., Sahu, A.
(2008). Hypothalamic Phosphatidylinositol 3-Kinase Pathway of Leptin Signaling Is Impaired during the Development of Diet-Induced Obesity in FVB/N Mice. Endocrinology
149: 1121-1128
[Abstract][Full Text]
Nusken, K.-D., Dotsch, J., Rauh, M., Rascher, W., Schneider, H.
(2008). Uteroplacental Insufficiency after Bilateral Uterine Artery Ligation in the Rat: Impact on Postnatal Glucose and Lipid Metabolism and Evidence for Metabolic Programming of the Offspring by Sham Operation. Endocrinology
149: 1056-1063
[Abstract][Full Text]
Juan, C.-C., Chuang, T.-Y., Lien, C.-C., Lin, Y.-J., Huang, S.-W., Kwok, C. F., Ho, L.-T.
(2008). Leptin increases endothelin type A receptor levels in vascular smooth muscle cells. Am. J. Physiol. Endocrinol. Metab.
294: E481-E487
[Abstract][Full Text]
Erdmann, J., Kallabis, B., Oppel, U., Sypchenko, O., Wagenpfeil, S., Schusdziarra, V.
(2008). Development of hyperinsulinemia and insulin resistance during the early stage of weight gain. Am. J. Physiol. Endocrinol. Metab.
294: E568-E575
[Abstract][Full Text]
Surmi, B. K., Atkinson, R. D., Gruen, M. L., Coenen, K. R., Hasty, A. H.
(2008). The role of macrophage leptin receptor in aortic root lesion formation. Am. J. Physiol. Endocrinol. Metab.
294: E488-E495
[Abstract][Full Text]
Schwartz, A. R., Patil, S. P., Laffan, A. M., Polotsky, V., Schneider, H., Smith, P. L.
(2008). Obesity and Obstructive Sleep Apnea: Pathogenic Mechanisms and Therapeutic Approaches. Proc Am Thorac Soc
5: 185-192
[Abstract][Full Text]
Badellino, K. O., Wolfe, M. L., Reilly, M. P., Rader, D. J.
(2008). Endothelial Lipase Is Increased In Vivo by Inflammation in Humans. Circulation
117: 678-685
[Abstract][Full Text]
Augustine, R. A., Ladyman, S. R., Grattan, D. R.
(2008). From feeding one to feeding many: hormone-induced changes in bodyweight homeostasis during pregnancy. J. Physiol.
586: 387-397
[Abstract][Full Text]
Kosmiski, L. A., Bacchetti, P., Kotler, D. P., Heymsfield, S. B., Lewis, C. E., Shlipak, M. G., Scherzer, R., Grunfeld, C.
(2008). Relationship of Fat Distribution with Adipokines in Human Immunodeficiency Virus Infection. J. Clin. Endocrinol. Metab.
93: 216-224
[Abstract][Full Text]
Francois, F, Roper, J, Goodman, A J, Pei, Z, Ghumman, M, Mourad, M, de Perez, A Z O., Perez-Perez, G I, Tseng, C-H, Blaser, M J
(2008). The association of gastric leptin with oesophageal inflammation and metaplasia. Gut
57: 16-24
[Abstract][Full Text]
Hanaoka, M., Yu, X., Urushihata, K., Ota, M., Fujimoto, K., Kubo, K.
(2008). Leptin and Leptin Receptor Gene Polymorphisms in Obstructive Sleep Apnea Syndrome. Chest
133: 79-85
[Abstract][Full Text]
Chia, V. M., Newcomb, P. A., Lampe, J. W., White, E., Mandelson, M. T., McTiernan, A., Potter, J. D.
(2007). Leptin Concentrations, Leptin Receptor Polymorphisms, and Colorectal Adenoma Risk. Cancer Epidemiol. Biomarkers Prev.
16: 2697-2703
[Abstract][Full Text]
Harsch, I. A.
(2007). Metabolic disturbances in patients with obstructive sleep apnoea syndrome. ERR
16: 196-202
[Abstract][Full Text]
Baicy, K., London, E. D., Monterosso, J., Wong, M.-L., Delibasi, T., Sharma, A., Licinio, J.
(2007). From the Cover: Leptin replacement alters brain response to food cues in genetically leptin-deficient adults. Proc. Natl. Acad. Sci. USA
104: 18276-18279
[Abstract][Full Text]
DiMarco, N. M., Dart, L., Sanborn, C.
(2007). Modified activity-stress paradigm in an animal model of the female athlete triad. J. Appl. Physiol.
103: 1469-1478
[Abstract][Full Text]
Djurovic, S., Berge, K. E., Birkenes, B., Braaten, O., Retterstol, L.
(2007). The effect of red wine on plasma leptin levels and vasoactive factors from adipose tissue: A randomized crossover trial. Alcohol Alcohol
42: 525-528
[Abstract][Full Text]
Chung, B., Matak, P., McKie, A. T., Sharp, P.
(2007). Leptin Increases the Expression of the Iron Regulatory Hormone Hepcidin in HuH7 Human Hepatoma Cells. J. Nutr.
137: 2366-2370
[Abstract][Full Text]
Bodary, P. F.
(2007). Links Between Adipose Tissue and Thrombosis in the Mouse. Arterioscler. Thromb. Vasc. Bio.
27: 2284-2291
[Abstract][Full Text]
Mokhlesi, B., Tulaimat, A.
(2007). Recent Advances in Obesity Hypoventilation Syndrome. Chest
132: 1322-1336
[Abstract][Full Text]
Fujimoto, W., Shiuchi, T., Miki, T., Minokoshi, Y., Takahashi, Y., Takeuchi, A., Kimura, K., Saito, M., Iwanaga, T., Seino, S.
(2007). Dmbx1 is essential in agouti-related protein action. Proc. Natl. Acad. Sci. USA
104: 15514-15519
[Abstract][Full Text]
Yang, R., Barouch, L. A.
(2007). Leptin Signaling and Obesity: Cardiovascular Consequences. Circ. Res.
101: 545-559
[Abstract][Full Text]
Morton, G. J.
(2007). Hypothalamic leptin regulation of energy homeostasis and glucose metabolism. J. Physiol.
583: 437-443
[Abstract][Full Text]
Kojima, C. J., Carroll, J. A., Matteri, R. L., Touchette, K. J., Allee, G. L.
(2007). Effects of weaning and weaning weight on neuroendocrine regulators of feed intake in pigs. J ANIM SCI
85: 2133-2139
[Abstract][Full Text]
Lopaschuk, G. D., Folmes, C. D.L., Stanley, W. C.
(2007). Cardiac Energy Metabolism in Obesity. Circ. Res.
101: 335-347
[Abstract][Full Text]
Campo, A., Fruhbeck, G., Zulueta, J. J., Iriarte, J., Seijo, L. M., Alcaide, A. B., Galdiz, J. B., Salvador, J.
(2007). Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients. Eur Respir J
30: 223-231
[Abstract][Full Text]
Axler, O., Ahnstrom, J., Dahlback, B.
(2007). An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma. J. Lipid Res.
48: 1772-1780
[Abstract][Full Text]
Hayes, M. R., Miller, C. K., Ulbrecht, J. S., Mauger, J. L., Parker-Klees, L., Gutschall, M. D., Mitchell, D. C., Smiciklas-Wright, H., Covasa, M.
(2007). A Carbohydrate-Restricted Diet Alters Gut Peptides and Adiposity Signals in Men and Women with Metabolic Syndrome. J. Nutr.
137: 1944-1950
[Abstract][Full Text]
Harris, R. B. S., Mitchell, T. D., Kelso, E. W., Flatt, W. P.
(2007). Changes in environmental temperature influence leptin responsiveness in low- and high-fat-fed mice. Am. J. Physiol. Regul. Integr. Comp. Physiol.
293: R106-R115
[Abstract][Full Text]
Guerra, B., Santana, A., Fuentes, T., Delgado-Guerra, S., Cabrera-Socorro, A., Dorado, C., Calbet, J. A. L.
(2007). Leptin receptors in human skeletal muscle. J. Appl. Physiol.
102: 1786-1792
[Abstract][Full Text]
Aoyagi, T., Birumachi, J.-i., Hiroyama, M., Fujiwara, Y., Sanbe, A., Yamauchi, J., Tanoue, A.
(2007). Alteration of Glucose Homeostasis in V1a Vasopressin Receptor-Deficient Mice. Endocrinology
148: 2075-2084
[Abstract][Full Text]
Doyon, C., Samson, P., Lalonde, J., Richard, D.
(2007). Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats. J Endocrinol
193: 11-19
[Abstract][Full Text]
Ruhl, C. E, Harris, T. B, Ding, J., Goodpaster, B. H, Kanaya, A. M, Kritchevsky, S. B, Simonsick, E. M, Tylavsky, F. A, Everhart, J. E, for the Health ABC Study,
(2007). Body mass index and serum leptin concentration independently estimate percentage body fat in older adults. Am. J. Clin. Nutr.
85: 1121-1126
[Abstract][Full Text]
Fleisch, A. F., Agarwal, N., Roberts, M. D., Han, J. C., Theim, K. R., Vexler, A., Troendle, J., Yanovski, S. Z., Yanovski, J. A.
(2007). Influence of Serum Leptin on Weight and Body Fat Growth in Children at High Risk for Adult Obesity. J. Clin. Endocrinol. Metab.
92: 948-954
[Abstract][Full Text]
Skurk, T., Alberti-Huber, C., Herder, C., Hauner, H.
(2007). Relationship between Adipocyte Size and Adipokine Expression and Secretion. J. Clin. Endocrinol. Metab.
92: 1023-1033
[Abstract][Full Text]
Lee, M.-J., Wang, Y., Ricci, M. R., Sullivan, S., Russell, C. D., Fried, S. K.
(2007). Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue. Am. J. Physiol. Endocrinol. Metab.
292: E858-E864
[Abstract][Full Text]
Jurczak, M. J., Danos, A. M., Rehrmann, V. R., Allison, M. B., Greenberg, C. C., Brady, M. J.
(2007). Transgenic overexpression of protein targeting to glycogen markedly increases adipocytic glycogen storage in mice. Am. J. Physiol. Endocrinol. Metab.
292: E952-E963
[Abstract][Full Text]
Krol, E., Speakman, J. R
(2007). Regulation of body mass and adiposity in the field vole, Microtus agrestis: a model of leptin resistance. J Endocrinol
192: 271-278
[Abstract][Full Text]
Bonomo, I. T., Lisboa, P. C., Pereira, A. R., Passos, M. C. F., de Moura, E. G.
(2007). Prolactin inhibition in dams during lactation programs for overweight and leptin resistance in adult offspring. J Endocrinol
192: 339-344
[Abstract][Full Text]
Li, J., Savransky, V., Nanayakkara, A., Smith, P. L., O'Donnell, C. P., Polotsky, V. Y.
(2007). Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia. J. Appl. Physiol.
102: 557-563
[Abstract][Full Text]
Pfluger, P. T., Kampe, J., Castaneda, T. R., Vahl, T., D'Alessio, D. A., Kruthaupt, T., Benoit, S. C., Cuntz, U., Rochlitz, H. J., Moehlig, M., Pfeiffer, A. F. H., Koebnick, C., Weickert, M. O., Otto, B., Spranger, J., Tschop, M. H.
(2007). Effect of Human Body Weight Changes on Circulating Levels of Peptide YY and Peptide YY3-36. J. Clin. Endocrinol. Metab.
92: 583-588
[Abstract][Full Text]
Ebihara, K., Kusakabe, T., Hirata, M., Masuzaki, H., Miyanaga, F., Kobayashi, N., Tanaka, T., Chusho, H., Miyazawa, T., Hayashi, T., Hosoda, K., Ogawa, Y., DePaoli, A. M., Fukushima, M., Nakao, K.
(2007). Efficacy and Safety of Leptin-Replacement Therapy and Possible Mechanisms of Leptin Actions in Patients with Generalized Lipodystrophy. J. Clin. Endocrinol. Metab.
92: 532-541
[Abstract][Full Text]
Scarpace, P. J., Matheny, M., Zhang, Y., Cheng, K.-Y., Tumer, N.
(2007). Leptin Antagonist Reveals an Uncoupling between Leptin Receptor Signal Transducer and Activator of Transcription 3 Signaling and Metabolic Responses with Central Leptin Resistance. J. Pharmacol. Exp. Ther.
320: 706-712
[Abstract][Full Text]
von Haehling, S., Doehner, W., Anker, S. D
(2007). Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure. Cardiovasc Res
73: 298-309
[Abstract][Full Text]
Power, C., Miller, S. K., Alpert, P. T.
(2007). Promising New Causal Explanations for Obesity and Obesity-Related Diseases. Biol Res Nurs
8: 223-233
[Abstract]
Chouri-Pontarollo, N., Borel, J.-C., Tamisier, R., Wuyam, B., Levy, P., Pepin, J.-L.
(2007). Impaired Objective Daytime Vigilance in Obesity-Hypoventilation Syndrome: Impact of Noninvasive Ventilation. Chest
131: 148-155
[Abstract][Full Text]
Polotsky, V. Y., O'Donnell, C. P.
(2007). Genomics of Sleep-disordered Breathing. Proc Am Thorac Soc
4: 121-126
[Abstract][Full Text]
Gao, J., Katagiri, H., Ishigaki, Y., Yamada, T., Ogihara, T., Imai, J., Uno, K., Hasegawa, Y., Kanzaki, M., Yamamoto, T. T., Ishibashi, S., Oka, Y.
(2007). Involvement of Apolipoprotein E in Excess Fat Accumulation and Insulin Resistance. Diabetes
56: 24-33
[Abstract][Full Text]
Srivastava, R. K., Krishna, A.
(2007). Adiposity associated rise in leptin impairs ovarian activity during winter dormancy in Vespertilionid bat, Scotophilus heathi. Reproduction
133: 165-176
[Abstract][Full Text]
Irani, B. G., Dunn-Meynell, A. A., Levin, B. E.
(2007). Altered Hypothalamic Leptin, Insulin, and Melanocortin Binding Associated with Moderate-Fat Diet and Predisposition to Obesity. Endocrinology
148: 310-316
[Abstract][Full Text]
Kavey, R.-E. W., Allada, V., Daniels, S. R., Hayman, L. L., McCrindle, B. W., Newburger, J. W., Parekh, R. S., Steinberger, J.
(2006). Cardiovascular Risk Reduction in High-Risk Pediatric Patients: A Scientific Statement From the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics. Circulation
114: 2710-2738
[Abstract][Full Text]
Woods, S. C., Benoit, S. C., Clegg, D. J.
(2006). The Brain-Gut-Islet Connection. Diabetes
55: S114-S121
[Abstract][Full Text]
Bell, L. N., Ward, J. L., Degawa-Yamauchi, M., Bovenkerk, J. E., Jones, R., Cacucci, B. M., Gupta, C. E., Sheridan, C., Sheridan, K., Shankar, S. S., Steinberg, H. O., March, K. L., Considine, R. V.
(2006). Adipose tissue production of hepatocyte growth factor contributes to elevated serum HGF in obesity. Am. J. Physiol. Endocrinol. Metab.
291: E843-E848
[Abstract][Full Text]
Mertens, I., Considine, R. V, Van der Planken, M., Van Gaal, L. F
(2006). Hemostasis and fibrinolysis in non-diabetic overweight and obese men and women. Is there still a role for leptin?. Eur J Endocrinol
155: 477-484
[Abstract][Full Text]
Lee, M.-J., Fried, S. K.
(2006). Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue. J. Lipid Res.
47: 1984-1993
[Abstract][Full Text]
Ogunwobi, O., Mutungi, G., Beales, I. L. P.
(2006). Leptin Stimulates Proliferation and Inhibits Apoptosis in Barrett's Esophageal Adenocarcinoma Cells by Cyclooxygenase-2-Dependent, Prostaglandin-E2-Mediated Transactivation of the Epidermal Growth Factor Receptor and c-Jun NH2-Terminal Kinase Activation. Endocrinology
147: 4505-4516
[Abstract][Full Text]
Gosman, G. G., Katcher, H. I., Legro, R. S.
(2006). Obesity and the role of gut and adipose hormones in female reproduction. Hum Reprod Update
12: 585-601
[Abstract][Full Text]
Phan, L. K., Chung, W. K., Leibel, R. L.
(2006). The mahoganoid mutation (Mgrn1md) improves insulin sensitivity in mice with mutations in the melanocortin signaling pathway independently of effects on adiposity. Am. J. Physiol. Endocrinol. Metab.
291: E611-E620
[Abstract][Full Text]
Jung, U. J., Lee, M.-K., Park, Y. B., Jeon, S.-M., Choi, M.-S.
(2006). Antihyperglycemic and Antioxidant Properties of Caffeic Acid in db/db Mice. J. Pharmacol. Exp. Ther.
318: 476-483
[Abstract][Full Text]
Kok, P., Roelfsema, F., Frolich, M., van Pelt, J., Meinders, A. E., Pijl, H.
(2006). Activation of Dopamine D2 Receptors Lowers Circadian Leptin Concentrations in Obese Women. J. Clin. Endocrinol. Metab.
91: 3236-3240
[Abstract][Full Text]
Banerjee, I., Trueman, J. A, Hall, C. M, Price, D. A, Patel, L., Whatmore, A. J, Hirschhorn, J. N, Read, A. P, Palmert, M. R, Clayton, P. E
(2006). Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphisms.. Eur J Endocrinol
155: 121-126
[Abstract][Full Text]
Gannage-Yared, M.-H., Khalife, S., Semaan, M., Fares, F., Jambart, S., Halaby, G.
(2006). Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men.. Eur J Endocrinol
155: 167-176
[Abstract][Full Text]
Hick, R. W., Gruver, A. L., Ventevogel, M. S., Haynes, B. F., Sempowski, G. D.
(2006). Leptin Selectively Augments Thymopoiesis in Leptin Deficiency and Lipopolysaccharide-Induced Thymic Atrophy. J. Immunol.
177: 169-176
[Abstract][Full Text]
Lorincz, A M, Sukumar, S
(2006). Molecular links between obesity and breast cancer.. Endocr Relat Cancer
13: 279-292
[Abstract][Full Text]
Langenberg, C., Bergstrom, J., Scheidt-Nave, C., Pfeilschifter, J., Barrett-Connor, E.
(2006). Cardiovascular Death and the Metabolic Syndrome: Role of adiposity-signaling hormones and inflammatory markers.. Diabetes Care
29: 1363-1369
[Abstract][Full Text]
Wagoner, B., Hausman, D. B., Harris, R. B. S.
(2006). Direct and indirect effects of leptin on preadipocyte proliferation and differentiation. Am. J. Physiol. Regul. Integr. Comp. Physiol.
290: R1557-R1564
[Abstract][Full Text]
Gelfand, E. V., Cannon, C. P.
(2006). Rimonabant: A Cannabinoid Receptor Type 1 Blocker for Management of Multiple Cardiometabolic Risk Factors. J Am Coll Cardiol
47: 1919-1926
[Abstract][Full Text]
Fliedner, S., Schulz, C., Lehnert, H.
(2006). Brain Uptake of Intranasally Applied Radioiodinated Leptin in Wistar Rats. Endocrinology
147: 2088-2094
[Abstract][Full Text]
Roberts, S. B., Rosenberg, I.
(2006). Nutrition and Aging: Changes in the Regulation of Energy Metabolism With Aging. Physiol. Rev.
86: 651-667
[Abstract][Full Text]
Haider, D. G., Schindler, K., Schaller, G., Prager, G., Wolzt, M., Ludvik, B.
(2006). Increased Plasma Visfatin Concentrations in Morbidly Obese Subjects Are Reduced after Gastric Banding. J. Clin. Endocrinol. Metab.
91: 1578-1581
[Abstract][Full Text]
Sood, A, Ford, E S, Camargo, C A Jr
(2006). Association between leptin and asthma in adults. Thorax
61: 300-305
[Abstract][Full Text]
Raju, S. V. Y., Zheng, M., Schuleri, K. H., Phan, A. C., Bedja, D., Saraiva, R. M., Yiginer, O., Vandegaer, K., Gabrielson, K. L., O'Donnell, C. P., Berkowitz, D. E., Barouch, L. A., Hare, J. M.
(2006). Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptin-resistant obesity.. Proc. Natl. Acad. Sci. USA
103: 4222-4227
[Abstract][Full Text]
Hahn, S., Haselhorst, U., Quadbeck, B., Tan, S., Kimmig, R., Mann, K., Janssen, O. E
(2006). Decreased soluble leptin receptor levels in women with polycystic ovary syndrome. Eur J Endocrinol
154: 287-294
[Abstract][Full Text]
Greenberg, A. S, Obin, M. S
(2006). Obesity and the role of adipose tissue in inflammation and metabolism. Am. J. Clin. Nutr.
83: 461S-465S
[Abstract][Full Text]
Hallschmid, M., Smolnik, R., McGregor, G., Born, J., Fehm, H. L.
(2006). Overweight Humans Are Resistant to the Weight-Reducing Effects of Melanocortin4-10. J. Clin. Endocrinol. Metab.
91: 522-525
[Abstract][Full Text]
Peters, J. H., Ritter, R. C., Simasko, S. M.
(2006). Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons. Am. J. Physiol. Cell Physiol.
290: C427-C432
[Abstract][Full Text]
Mancuso, P., Huffnagle, G. B., Olszewski, M. A., Phipps, J., Peters-Golden, M.
(2006). Leptin Corrects Host Defense Defects after Acute Starvation in Murine Pneumococcal Pneumonia. Am. J. Respir. Crit. Care Med.
173: 212-218
[Abstract][Full Text]
Barouch, L. A., Gao, D., Chen, L., Miller, K. L., Xu, W., Phan, A. C., Kittleson, M. M., Minhas, K. M., Berkowitz, D. E., Wei, C., Hare, J. M.
(2006). Cardiac Myocyte Apoptosis Is Associated With Increased DNA Damage and Decreased Survival in Murine Models of Obesity. Circ. Res.
98: 119-124
[Abstract][Full Text]
Johnston, R. A., Theman, T. A., Shore, S. A.
(2006). Augmented responses to ozone in obese carboxypeptidase E-deficient mice. Am. J. Physiol. Regul. Integr. Comp. Physiol.
290: R126-R133
[Abstract][Full Text]
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