Role of leptin in the neuroendocrine response to fasting

Ahima, Rexford S.; Prabakaran, Daniel; Mantzoros, Christos S.; Qu, Daqing; Lowell, Bradford B.; Maratos–Flier, Eleftheria; Flier, Jeffrey S.

doi:10.1038/382250a0

Cited by 2,893 publications

(2,309 citation statements)

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“…23 Jeff Flier and colleagues at the Beth Israel Hospital in Boston were the first to elegantly show that leptin was most likely to have evolved as a signal for Inheritance and human obesity S O'Rahilly and IS Farooqi starvation rather than nutrient excess, in that the rapid fall of leptin in the plasma seen upon fasting was necessary for the normal neurohormonal adaptations seen with starvation in mammals. 24 Mutations in single genes involved in the central control of energy balance can lead to human obesity At this stage in the mid-1990s, the relevance of leptin to human physiology was uncertain. As humans gain fat mass, in general the levels of leptin increase, 25 and this suggested that either leptin resistance was a major factor in human obesity or indeed that leptin was irrelevant to the control of human body weight.…”

Section: Discussionmentioning

confidence: 99%

Human obesity as a heritable disorder of the central control of energy balance

O’Rahilly

Farooqi

2008

Int J Obes

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In the spirit of celebration associated with the 20th anniversary of the Pennington Biomedical Research Center, we have seized the opportunity of taking a highly personal and not at all comprehensive 'whistle-stop tour' of a large body of evidence that, we feel, supports the following conclusions: (1) that body fat stores are regulated by biological control processes in humans as they are in lower animals; (2) that there are major inherited influences on the efficiency whereby such control processes operate in humans; (3) that the precise nature of those genetic and biological influences and how they interact with environmental factors are beginning to be understood; (4) that most of the genes discovered thus far have their principal impact on hunger, satiety and food intake; (5) that while there is understandable resistance to the notion that genes can influence a human behavior such as the habitual ingestion of food, the implications of these discoveries are essentially benign. Indeed, we hope that they may eventually lead to improved treatment for patients and, in addition, help to inculcate a more enlightened attitude to the obese with a reduction in their experience of social and economic discrimination.

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Section: Discussionmentioning

confidence: 99%

Human obesity as a heritable disorder of the central control of energy balance

O’Rahilly

Farooqi

2008

Int J Obes

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“…17,38,39 In rodents, leptin modulates thyroid hormone production in situations in which energy conservation through a reduction in metabolic rate is required. 40 Such effect appears to occur principally at the level of TRH neurons in the paraventricular hypothalamic nucleus (PVN). Leptin could act directly at receptors on the TRH neuron or indirectly through other hypothalamic neurons that project to the PVN.…”

Section: Discussionmentioning

confidence: 99%

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

et al. 2008

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Moderate obesity is known to be associated with multiple endocrine abnormalities. Less information is available on the hormonal status of patients with morbid obesity and on the effects of major weight loss. We studied 16 severely obese (BMI 40.6-69.9 kg/m 2 ) nondiabetic patients and 7 nonobese (BMI range 24.6-27.7 kg/m 2 ), sex-and age-matched healthy volunteers. During 24 h in a metabolic ward, four meals were administered and hourly blood samples were drawn from a central venous catheter for the measurement of glucose, insulin, leptin, thyrotropic hormone (TSH), growth hormone (GH) and prolactin. Insulin sensitivity was measured by a euglycaemic hyperinsulinaemic clamp. Studies were repeated 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach, which caused an average weight loss of 35±4 kg (or 26 ± 2% of initial weight). Compared with controls, patients were hyperinsulinaemic (290 ± 31 vs 88 ± 4 pmol l À1 , P ¼ 0.0002), insulin resistant (23.5±2.8 vs 52.9±4.9 mmol min À1 kg FFM À1 , P ¼ 0.0006) and hyperleptinaemic (52.5±5.8 vs 10.9±3 ng ml À1 , P ¼ 0.0002). Plasma TSH levels were increased throughout the day-night cycle (averaging 2.02 ± 0.18 vs 1.09 ± 0.19 mU ml À1 of controls, P ¼ 0.01), whereas serum GH levels were suppressed (0.46±0.10 vs 3.01±1.15, P ¼ 0.002). Following surgery, the hyperinsulinaemia and insulin resistance were fully normalized; in concomitance with a major drop in leptin levels (to 14.4±2.7 ng ml À1 , P ¼ 0.02), TSH decreased and GH increased to near-normal levels. In the whole dataset, mean 24-h leptin levels were directly related to mean 24-h TSH levels after controlling for confounders this relationship was lost only after adjusting for fat mass. We conclude that in morbid obesity leptin is a determinant of changes in pituitary function.

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“…It has been well characterised that in states of negative energy balance, such as prolonged fasting, regulation of the HPT axis is altered, as manifested by low plasma T3, and T4, with a low or inappropriately normal TSH and a reduction in TRH biosynthesis and secretion [1,5,9,15,16,25,27,33,51,64]. This central hypothyroidism following starvation may be an important adaptive response, by reducing thermogenesis and hence, reducing the obligatory use of energy stores [21].…”

Section: The Hpt Axis and Starvationmentioning

confidence: 99%