Obesity, leptin resistance, and the effects of insulin reduction

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 insulinsuppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (410%) and BMI (4À3 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.

Effects of Auricular Acupressure Combined with Low-Calorie Diet on the Leptin Hormone in Obese and Overweight Iranian Individuals

“…41 The high levels of leptin may result in leptin resistance which appears to be a major factor in obesity. [10][11][12] The main fi nding of this study is that acupressure reduced plasma levels of leptin in overweight and obese participants. Although Hsu et al studied the effects of auricular acupuncture on obese women, we included both genders.…”

“…12 The combination of the two mechanisms could explain the obesity: fi rst, the absence of leptin or its receptor leads to uncontrolled food intake in normal people; 2 5-8 second, the leptin resistance that is caused by defects in leptin receptors or the large increase in leptin signals in obese people. [10][11][12] However, obesity is now recognised as a low-grade infl ammatory state that affects iron metabolic pathways through the iron regulatory peptide hepcidin. 13 14 Leptin, as a positive regulator of hepcidin, may improve iron metabolism disorders in obese individuals.…”

Dietary and physical activity patterns in children with fatty liver

“…Some metabolic pathways relating to glutathione may be abnormal in childhood NAFLD: plasma levels of elevated oxidized glutathione (Nobili et al, 2005) or plasma glutathione peroxidase (Mandato et al, 2005) have been found. Hyperleptinemia suggested leptin resistance, typical of obesity (Lustig et al, 2004).…”

Exogenous Leptin Administered Intramuscularly Induces Sex Hormone Disorder and Ca Loss via Downregulation of <i>Gnrh</i> and PI3K Expression

“…innumerous studies have described a critical role for leptin (LeP) in the regulation of gonadal function, uterine physiology, pregnancy, and implantation [3,5,10]. LeP dysfunction in both animals and humans is associated with profound metabolic abnormalities including obesity, dyslipidemia and LeP resistance [27]. LeP or its receptor dysfunction is among the answers explaining anovulation during obesity that leads to reproductive problems such as infertility [6].…”