Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance

Abstract

Adipose tissue performs complex metabolic and endocrine functions. Among the endocrine products produced by adipose tissue are tumour necrosis factor α, interleukin 6, acylationstimulating protein and leptin. The present review will focus primarily on mechanisms regulating leptin production and leptin action, and the implications of this regulation in the control of energy balance. Leptin acts in the central nervous system where it interacts with a number of hypothalamic neuropeptide systems to regulate feeding behaviour and energy expenditure. The presence of extreme obesity in animals and human subjects with mutations of the leptin gene or the leptin receptor demonstrates that normal leptin production and action are critical for maintaining energy balance. Insulin is the major regulator of leptin production by adipose tissue. Insulin infusions increase circulating leptin concentrations in human subjects. Plasma leptin levels are markedly decreased in insulin-deficient diabetic rodents, and the low leptin levels contribute to diabetic hyperphagia. Based on in vitro studies, the effect of insulin to stimulate leptin production appears to involve increased glucose metabolism. Blockade of glucose transport or glycolysis inhibits leptin expression and secretion in isolated adipocytes. Evidence suggests that anaerobic metabolism of glucose to lactate does not stimulate leptin production. Alterations in insulin-mediated glucose metabolism in adipose tissue are likely to mediate the effects of energy restriction to decrease, and refeeding to increase, circulating leptin levels. Changes in glucose metabolism may also explain the observation that high-fat meals lower 24 h circulating leptin levels relative to high-carbohydrate meals in human subjects, suggesting a mechanism that may contribute to the effects that high-fat diets have in promoting increased energy intake, weight gain and obesity. The decreased circulating leptin observed during energy restriction is related to increased sensations of hunger in human subjects. Thus, decreases in leptin during energyrestricted weight-loss regimens may contribute to the strong propensity for weight regain. A better understanding of the precise mechanisms regulating leptin production and leptin action may lead to new approaches for managing obesity.

Alimentação de suínos em terminação com dietas contendo ractopamina e extratos cítricos: desempenho e características de carcaça

“…A ingestão alimentar é influenciada por vários hormônios, dentre eles a leptina. A síntese de leptina é diretamente proporcional ao acúmulo de tecido adiposo (HAVEL, 2000). As ações catabólicas do tecido adiposo são reguladas pelo sistema nervoso simpático (PÉNICAUD et al, 2000).…”

“…As ações catabólicas do tecido adiposo são reguladas pelo sistema nervoso simpático (PÉNICAUD et al, 2000). Assim, se a inervação simpática for ativada pelos agonistas beta-adrenérgicos, há redução da expressão gênica da leptina (HAVEL, 2000). Essa inibição da expressão gênica da leptina pelo uso da ractopamina pode ter ocorrido com os animais utilizados neste trabalho, justificando, assim, a ausência de redução no consumo alimentar.…”

Effects of physical activity on food intake

“…Many of the compensating mechanisms previously suggested like body temperature, 27,38,39 blood lipids, 40,41 glucose or insulin concentrations, 40,42 might well come into play on a shortterm basis. Long-term regulatory mechanisms like adipose tissue-related factors such as leptin 43,44 are also known now. But for periods around 3-7 days no good physiological mechanisms are yet available.…”

Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex

“…Android body fat distribution is associated with insulin resistance more than is a gynoid body fat distribution [5], with the site of abdominal fat distribution being an additional determinant of insulin sensitivity [6,7,8,9,10,11]. We found in both lean and obese subjects that the intraabdominal fat (IAF) depot is a stronger determinant of insulin sensitivity than the subcutaneous fat (SCF) depot [11], while SCF is the main determinant of the plasma concentration of leptin [11], an adipocyte-derived hormone regulating energy metabolism [12,13]. …”

“…Unlike many of the other "adipokines" such as tumour necrosis factor-α (TNF-α), leptin and resistin that increase with adiposity [13], circulating adiponectin concentrations are reduced in individuals who are obese [28,29,30,31], have cardiovascular disease [32] or Type 2 diabetes [29]. Circulating adiponectin concentrations are correlated with insulin sensitivity [30,31], with low concentrations predicting a future decrease in insulin sensitivity in Pima Indians [33].…”