Obesity, leptin resistance, and the effects of insulin reduction

Department of Pediatrics, University of California, San Francisco, CA 94143-0434, USA.
International Journal of Obesity (Impact Factor: 5.39). 10/2004; 28(10):1344-8. DOI: 10.1038/sj.ijo.0802753
Source: PubMed

ABSTRACT Leptin resistance is a hallmark of obesity, but its etiology is unknown, and its clinical measurement is elusive. Leptin-sensitive subjects have normal resting energy expenditure (REE) at a low leptin concentration, while leptin-resistant subjects have a normal REE at a higher leptin concentration; thus, the ratio of REE:Leptin may provide a surrogate index of leptin sensitivity. We examined changes in REE and leptin in a cohort of 17 obese subjects during experimental weight loss therapy with the insulin-suppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (>10%) and BMI (>-3 kg/m(2)) with a 34% decline in leptin and a 46% decrease in insulin area under the curve (IAUC) to oral glucose tolerance testing. These subjects maintained their pretreatment REE, and thus exhibited a rise in REE:Leptin, while the other 11 showed minimal changes in each of these parameters. For the entire cohort, the change in IAUC correlated negatively with the change in REE:Leptin. These results suggest that the REE:Leptin ratio, while derivative, may serve as a useful clinical indicator of changes in leptin sensitivity within obese subjects. They also support the possibilities that hyperinsulinemia may be a proximate cause of leptin resistance, and that reduction of insulinemia may promote weight loss by improving leptin sensitivity.

  • Source
    • "Neither were significant differences in body weight found in female offspring of moderate protein-restricted rats (30%) during gestation at the age of 24 weeks, although they did exhibit significantly greater food intake than their controls (Ikenasio-Thorpe et al., 2007). Central and peripheral resistance to insulin and/or leptin signaling have been proposed as important mechanisms responsible for the deregulation of energy homeostasis, which may lead to obesity (Levin and Dunn-Meynell, 2002; Lustig et al., 2004; Esteghamati et al., 2009; Palou et al., 2010a) (see below). On the other hand, adiponectin, which has been described as an important adipokine related with obesity and insulin sensitivity , may also play a role in the early programming mechanisms involved in the effects of gestational undernutrition, as it exerts important effects on carbohydrate metabolism, improving "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies in humans and controlled intervention studies in animals have shown that nutritional programming in early periods of life is a phenomenon that affects metabolic and physiological functions throughout life. The phenotypes of health or disease are hence the result of the interaction between genetic and environmental factors, starting right from conception. In this sense, gestation and lactation are disclosed as critical periods. Continuous food restriction during these stages may lead to permanent adaptations with lasting effects on the metabolism of the offspring and may influence the propensity to develop different chronic diseases associated with obesity. However, the different outcomes of these adaptations on later health may depend on factors such as the type, duration, period, and severity of the exposure to energy restriction conditions, and they are, in part, gender specific. A better understanding of the factors and mechanisms involved in metabolic programming, and their effects, may contribute significantly to the prevention of obesity, which is considered to be one of the major health concerns of our time. Here, the different outcomes of maternal food restriction during gestation and lactation in the metabolic health of offspring, as well as potential mechanisms underlying these effects are reviewed.
    Frontiers in Physiology 11/2012; 3:436. DOI:10.3389/fphys.2012.00436 · 3.50 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to determine whether physical activity stimulates GLP-1 release on the short-term in normal weight and in obese subjects compared to rest and, furthermore, whether modest weight loss affects GLP-1 release or sensitivity in the obese. Normal weight (n=28; 12 males, 16 females; BMI 22.9+/-1.4; age 35+/-12.7), as well as obese subjects (n=27; 21 males, 6 females; BMI 30.9+/-2.7; age 47.1+/-11.86) were tested in a resting and a physical activity condition. Obese subjects were matched over two groups for a weight loss period of 3 months. After weight loss, the tests were repeated. The area under the curve (AUC pmol/lxmin) for GLP-1 concentrations was significantly increased in the physical activity condition compared to rest in lean subjects (P=0.05) as well as in the obese subjects after weight loss (P<0.05), but not in the obese subjects before weight loss. Physical activity-stimulated GLP-1 release in lean and obese subjects after a weight loss period supports the idea of a neuroendocrine loop in addition to distal-intestinal stimulation of GLP-1 release. Modest weight loss might be effective for increasing GLP-1 sensitivity to acute stimulation.
    Physiology & Behavior 01/2005; 83(3):459-66. DOI:10.1016/j.physbeh.2004.08.035 · 3.03 Impact Factor
Show more


Available from