Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone

Russell, Colleen D.; Petersen, R. N.; Rao, S. P.; Ricci, Matthew; Prasad, Amit; Zhang, Y.; Brolin, Robert E.; Fried, Susan K.

doi:10.1152/ajpendo.1998.275.3.e507

Cited by 138 publications

(151 citation statements)

References 30 publications

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“…No correlation was found between 4 weeks reduction in weight and the concomitant reduction in leptin, whereas 32% of the variation in the change in leptin after 24 weeks could be accounted for by variation in total weight loss. These findings support the notion that plasma leptin level is a marker of nutritional status, reflecting both the size of FM per se and current energy balance (43,44). Although it is well-established that exogenously administrated leptin increases EE and physical activity in rodents, there seems to be some difficulty in proving a role of endogenous leptin in the regulation of EE in humans, and findings are not consistent.…”

Section: Discussionmentioning

confidence: 48%

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

et al. 2001

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Objective: To examine the relationship between fasting plasma leptin and 24-hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention. Research Methods and Procedures: Twenty-one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m 2 ) and 13 lean (body mass index: 20.4 to 24.7 kg/m 2 ) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1-23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty-four-hour EE and substrate oxidations were measured by whole-body indirect calorimetry. SPA was assessed by microwave radar. Results: In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24-hour EE before (r ϭ Ϫ0.56, p Ͻ 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24-hour and resting nonprotein respiratory quotient (r ϭ Ϫ0.47, p Ͻ 0.05 and r ϭ Ϫ0.50, p Ͻ 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r ϭ Ϫ0.41, p ϭ 0.07), 16 weeks (r ϭ Ϫ0.51, p Ͻ 0.05), and 24 weeks (r ϭ Ϫ0.50, p Ͻ 0.05). Discussion: The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.

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Section: Discussionmentioning

confidence: 48%

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

et al. 2001

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“…There is evidence that different adipose tissue depots contribute disproportionately to circulating leptin concentrations. Thus, leptin secretion is greater in subcutaneous than in omental adipose tissue of obese subjects, 34,35 although no difference is observed in non-obese subjects. 36 It is therefore possible that the elevated insulin-stimulated leptin levels in the early-protein-restricted rats reflect enhanced rates of insulin-stimulated glucose uptake in the subcutaneous adipose tissue depot.…”

Section: Discussionmentioning

confidence: 87%

Enhanced glucose uptake into adipose tissue induced by early growth restriction augments excursions in plasma leptin response evoked by changes in insulin status

Holness

2001

Int J Obes

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OBJECTIVE:The study used a rat model of moderate protein restriction exclusively during fetal and early neonatal life, which has been established to cause intrauterine early growth retardation, to investigate possible association between adipocyte glucose utilisation and leptin secretion in vivo. DESIGN: These rats, termed early protein restricted, were transferred to a diet containing the standard amount of protein at weaning and remained on this diet until adulthood, at which time adipocyte glucose utilisation and leptin secretion was compared with that of age-matched controls. Insulin status was modulated by acute (2 h) insulin infusion at a constant rate (4.2 mU=min per kg) to elevate insulin to the high physiological range. Euglycaemia was maintained by variable glucose infusion. MEASUREMENTS: Glucose utilisation was measured in vivo in conscious unrestrained rats using 2-deoxy[1-3 H] glucose. Leptin concentrations (measured by radioimmunoassay) and whole-body glucose kinetics (measured using [3-3 H] glucose) were studied in the postabsorptive state and after acute insulin stimulation. RESULTS: Adipose-tissue glucose utilisation rates in vivo tended to be higher in the post-absorptive state and were consistently 1.8 -3.0-fold higher after insulin stimulation in the early-protein-restricted group compared with the control group. Both the absolute increase in leptin concentration elicited by hyperinsulinaemia and the magnitude of the effect of insulin to elevate plasma leptin levels were greater in the early-protein-restricted group compared with the control group (by 2.2-fold and 1.6-fold, respectively). The effect of insulin to stimulate R d was much greater in the early-protein-restricted group (4.1-fold) than in the control group (2.2-fold) and the absolute increase in R d elicited by insulin was 43% higher in the early-protein-restricted group than in the control group.

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“…21,22 In multiple forward stepwise regression analyses, circulating concentrations of insulin were significantly related to VAT, but not SAT, in males, and to SAT, but not VAT, in females. If insulin was not included as a covariate, then circulating concentrations of leptin were significantly correlated with both SAT and VAT in males, but only with SAT in females.…”

Section: Resultsmentioning

confidence: 99%

Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution

et al. 2001

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BACKGROUND: Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. METHODS: We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. RESULTS: Body composition by DEXA and MRI were highly correlated (r 2 ¼ 0.97, P < 0.0001). There were significant gender effects on leptin=total fat mass (males, 0.17 AE 0.01 ng=ml=kg; females, 0.49 AE 0.05 ng=ml=kg; P < 0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT=VAT; males, 12.3 AE 1.5; females, 32.9 AE 3.2; P < 0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P ¼ 0.001), SAT (P < 0.0001) and gender (P ¼ 0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. CONCLUSIONS: The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and=or primary genetic differences that are independent of amounts of VAT or SAT.

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Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone

Cited by 138 publications

References 30 publications

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

Enhanced glucose uptake into adipose tissue induced by early growth restriction augments excursions in plasma leptin response evoked by changes in insulin status

Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution

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