Obesity, leptin resistance, and the effects of insulin reduction.
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.
Department of Pediatrics, University of California, San Francisco, CA 94143-0434, USA. rlustig@peds.ucsf.edu
R H
RH
Lustig
S
S
Sen
J E
JE
Soberman
P A
PA
Velasquez-Mieyer
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D004734:Energy Metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D015282:Octreotide / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D015282:Octreotide