Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice

Mantzoros, C. S.; Qu, D.; Frederich, Robert; Susulic, V. S.; Lowell, B. B.; Maratos–Flier, Eleftheria; Flier, Jeffrey S.

doi:10.2337/diabetes.45.7.909

Cited by 106 publications

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“…The decrease in leptin during circadian misalignment could not be explained by a simultaneous decrease in the measured variables that have been shown to stimulate leptin secretion, namely glucose, insulin, cortisol, vagal tone, or food intake; or by an increase in those measured variables that can inhibit leptin: epinephrine, norepinephrine, or metabolic rate; or by a change in metabolic substrate (as suggested by respiratory exchange ratio) (30)(31)(32). Both short-term experimental sleep restriction (33) and chronic self-reported short sleep duration (34) are associated with decreased leptin, so the decrease in sleep during circadian misalignment in the current study may contribute to the decrease in leptin.…”

Section: Potential Mechanisms Involved In Effects Of Circadian Misalimentioning

confidence: 99%

Adverse metabolic and cardiovascular consequences of circadian misalignment

Scheer

Hilton

Mantzoros

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,843

1,489

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There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/ feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h ''day.'' Subjects ate 4 isocaloric meals each 28-h ''day.'' For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling Ϸ1,000 assays/ subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept Ϸ12 h out of phase from their habitual times, systematically decreased leptin (؊17%, P < 0.001), increased glucose (؉6%, P < 0.001) despite increased insulin (؉22%, P ‫؍‬ 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (؉3%, P ‫؍‬ 0.001), and reduced sleep efficiency (؊20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work. autonomic nervous system ͉ diabetes ͉ glucose metabolism ͉ leptin ͉ obesity A pproximately 8.6 million Americans perform shift work (1), which is associated with increased risk of obesity, diabetes, and cardiovascular disease (2-6). The endogenous circadian timing system, including the suprachiasmatic nucleus (SCN) in the hypothalamus and peripheral oscillators in vital organs, optimally regulates much of our physiology and behavior across the 24-h day when it is properly aligned with the sleep/wake cycle. However, shift work is generally associated with chronic misalignment between the endogenous circadian timing system and the behavioral cycles, including sleep/wake and fasting/ feeding cycles (7,8). Shift workers often experience symptoms akin to jet lag, with gastrointestinal complaints, fatigue, and sleepiness during the scheduled wake periods, and poor sleep during the daytime sleep attempts (9). Moreover, chronic circadian misalignment has been proposed to be the underlying cause for the adverse metabolic and cardiovascular health effects of shift work (10, 11). The SCN regulates circadian rhythms in leptin, plasma glucose, glucose tolerance, corticosteroids, and ...

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Section: Potential Mechanisms Involved In Effects Of Circadian Misalimentioning

confidence: 99%

Adverse metabolic and cardiovascular consequences of circadian misalignment

Scheer

Hilton

Mantzoros

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,843

1,489

View full text Add to dashboard Cite

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“…TZDs consistently suppress leptin expression in rodent fat in vivo and in vitro (Table 1) [113,114,115,116]. Furthermore, β-adrenergic activation rapidly decreases leptin expression and secretion in primary adipocytes in vitro and mice in vivo (Table 1) [117,118]. Insulin is a potent activator of leptin mRNA expression and protein secretion [49] and it is plausible that insulin is the major mediator of increased post-prandial leptin concentrations (Table 1) [119,120,121].…”

Section: Leptinmentioning

confidence: 99%

Regulation of adipocytokines and insulin resistance

2003

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It has long been known that obesity and insulin resistance are linked. Recently, it has been shown that adipocytes secrete several proteins including tumour necrosis factor-α, interleukin-6, resistin, and adiponectin. Since several of these so-called adipocytokines influence insulin sensitivity and glucose metabolism profoundly, they might provide a molecular link between increased adiposity and impaired insulin sensitivity. Thiazolidinediones which decrease insulin resistance and are used in the treatment of Type 2 diabetes seem to mediate part of their insulin-sensitising effects via modulation of adipocytokine expression.Furthermore, hormones such as β-adrenergic agonists, insulin, glucocorticoids, and growth hormone might impair insulin sensitivity at least in part via up-regulation or down-regulation of adipocytokine synthesis. We summarise the current knowledge on how major adipocyte-secreted proteins are regulated by hormones and drugs influencing insulin sensitivity and discuss its implications for insulin resistance and obesity. [Diabetologia (2003[Diabetologia ( ) 46:1594[Diabetologia ( -1603

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“…One proposed hypothesis is through changes in hypothalamic control of autonomic nervous system activity, 7 including changes in the balance of cholinergic (parasympathetic) and sympathetic tone, which have been shown to influence leptin and ghrelin secretion. 17,18 We used data from a randomized trial of moderateintensity physical activity among obese, sedentary postmenopausal women to investigate associations between exercise, sleep, body mass index (BMI), ghrelin, leptin and weight change. First, we examined whether sleep measures were associated with BMI, ghrelin and leptin at baseline.…”

Section: Introductionmentioning

confidence: 99%

Sleep, ghrelin, leptin and changes in body weight during a 1-year moderate-intensity physical activity intervention

et al. 2006

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Objective: To investigate cross-sectional and longitudinal relationships among exercise, sleep, ghrelin and leptin. Methods: We randomly assigned 173 post-menopausal sedentary overweight (body mass index X24.0 kg/m 2 and 433% body fat) women aged 50-75 years living in western Washington State to either a facility-and home-based moderate-intensity physical activity intervention or a stretching control group. Fasting plasma ghrelin, leptin, measured height, weight and selfreported sleep were assessed at baseline and 12 months. Results: There were no consistent cross-sectional patterns between self-reported sleep measures and ghrelin or leptin at baseline. The weight loss differences between exercisers and stretchers were greater for those who slept less at follow-up than at baseline compared to those whose sleep duration did not change (À3.2 kg, 95% confidence interval (CI) À5.8, À0.5). Improvements in sleep quality were associated with significantly greater differences between exercisers and stretchers for ghrelin increases (improved vs same sleep quality: þ 115 pg/ml, 95% CI þ 25, þ 206) and leptin decreases (improved vs worsened sleep quality: À5.7 ng/ml, 95% CI À9.5, À1.5). Conclusion: There was only limited evidence that changes in sleep duration or quality modified exercise-induced changes in weight, ghrelin or leptin. Moreover, the observed differences were not in the directions hypothesized. Future longitudinal studies including population-based samples using objective measures of sleep and long follow-up may help to clarify these relationships.

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Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice

Cited by 106 publications

References 0 publications

Adverse metabolic and cardiovascular consequences of circadian misalignment

Adverse metabolic and cardiovascular consequences of circadian misalignment

Regulation of adipocytokines and insulin resistance

Sleep, ghrelin, leptin and changes in body weight during a 1-year moderate-intensity physical activity intervention

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