Obesity, leptin resistance, and the effects of insulin reduction

R. H. Lustig, Saunak Sen, J. E. Soberman, P. A. Velasquez-Mieyer

Research output: Contribution to journalArticle

59 Citations (Scopus)

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 (>-3kg/m2) 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.

Original languageEnglish (US)
Pages (from-to)1344-1348
Number of pages5
JournalInternational Journal of Obesity
Volume28
Issue number10
DOIs
StatePublished - Oct 1 2004

Fingerprint

Leptin
Insulin Resistance
Obesity
Energy Metabolism
Insulin
Area Under Curve
Weight Loss
Octreotide
Hyperinsulinism
Glucose Tolerance Test

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Obesity, leptin resistance, and the effects of insulin reduction. / Lustig, R. H.; Sen, Saunak; Soberman, J. E.; Velasquez-Mieyer, P. A.

In: International Journal of Obesity, Vol. 28, No. 10, 01.10.2004, p. 1344-1348.

Research output: Contribution to journalArticle

Lustig, R. H. ; Sen, Saunak ; Soberman, J. E. ; Velasquez-Mieyer, P. A. / Obesity, leptin resistance, and the effects of insulin reduction. In: International Journal of Obesity. 2004 ; Vol. 28, No. 10. pp. 1344-1348.
@article{1c16703a4c6c41b38263380f1ff1705b,
title = "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 insulin-suppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (> 10{\%}) and BMI (>-3kg/m2) 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.",
author = "Lustig, {R. H.} and Saunak Sen and Soberman, {J. E.} and Velasquez-Mieyer, {P. A.}",
year = "2004",
month = "10",
day = "1",
doi = "10.1038/sj.ijo.0802753",
language = "English (US)",
volume = "28",
pages = "1344--1348",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Obesity, leptin resistance, and the effects of insulin reduction

AU - Lustig, R. H.

AU - Sen, Saunak

AU - Soberman, J. E.

AU - Velasquez-Mieyer, P. A.

PY - 2004/10/1

Y1 - 2004/10/1

N2 - 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 (>-3kg/m2) 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.

AB - 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 (>-3kg/m2) 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.

UR - http://www.scopus.com/inward/record.url?scp=6044270502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6044270502&partnerID=8YFLogxK

U2 - 10.1038/sj.ijo.0802753

DO - 10.1038/sj.ijo.0802753

M3 - Article

VL - 28

SP - 1344

EP - 1348

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 10

ER -