Insulin-sensitive obesity

Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E506-15. doi: 10.1152/ajpendo.00586.2009. Epub 2010 Jun 22.

Abstract

The association between obesity and impaired insulin sensitivity has long been recognized, although a subgroup of obese individuals seems to be protected from insulin resistance. In this study, we systematically studied differences in adipose tissue biology between insulin-sensitive (IS) and insulin-resistant (IR) individuals with morbid obesity. On the basis of glucose infusion rate during euglycemic hyperinsulinemic clamps, 60 individuals with a BMI of 45 +/- 1.3 kg/m(2) were divided into an IS and IR group matched for age, sex, and body fat prior to elective surgery. We measured fat distribution, circulating adipokines, and parameters of inflammation, glucose, and lipid metabolism and characterized adipose tissue morphology, function, and mRNA expression in abdominal subcutaneous (sc) and omental fat. IS compared with IR obese individuals have significantly lower visceral fat area (138 +/- 27 vs. 316 +/- 91 cm(2)), number of macrophages in omental adipose tissue (4.9 +/- 0.8 vs. 13.2 +/- 1.4%), mean omental adipocyte size (528 +/- 76 vs. 715 +/- 81 pl), circulating C-reactive protein, progranulin, chemerin, and retinol-binding protein-4 (all P values <0.05), and higher serum adiponectin (6.9 +/- 3.4 vs. 3.4 +/- 1.7 ng/ml) and omental adipocyte insulin sensitivity (all P values <0.01). The strongest predictors of insulin sensitivity by far were macrophage infiltration together with circulating adiponectin (r(2) = 0.98, P < 0.0001). In conclusion, independently of total body fat mass, increased visceral fat accumulation and adipose tissue dysfunction are associated with IR obesity. This suggests that mechanisms beyond a positive caloric balance such as inflammation and adipokine release determine the pathological metabolic consequences in patients with obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipokines / blood
  • Adipokines / genetics
  • Adult
  • Blood Glucose / metabolism
  • Body Composition / physiology
  • C-Reactive Protein / metabolism
  • Chemokines / blood
  • Chemokines / genetics
  • Female
  • Glucose Clamp Technique
  • Humans
  • Insulin Resistance / physiology*
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intra-Abdominal Fat / cytology
  • Intra-Abdominal Fat / metabolism*
  • Male
  • Middle Aged
  • Obesity, Morbid / metabolism*
  • Progranulins
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retinol-Binding Proteins, Plasma / genetics
  • Retinol-Binding Proteins, Plasma / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Subcutaneous Fat / cytology
  • Subcutaneous Fat / metabolism*

Substances

  • Adipokines
  • Blood Glucose
  • Chemokines
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • RBP4 protein, human
  • RNA, Messenger
  • Retinol-Binding Proteins, Plasma
  • chemerin protein, human
  • C-Reactive Protein