Adipose Tissue Hypoxia, Inflammation and Fibrosis in Obese Insulin Sensitive and Obese Insulin Resistant Subjects.

Adipose Tissue Hypoxia, Inflammation and Fibrosis in Obese Insulin Sensitive and Obese Insulin Resistant Subjects.

J Clin Endocrinol Metab. 2016 Feb 12;:jc20154125

Authors: Lawler HM, Underkofler CM, Kern PA, Erickson C, Bredbeck B, Rasouli N

Abstract
CONTEXT: A substantial number of obese individuals are relatively insulin sensitive and the etiology for this variation remains unknown.
OBJECTIVE: The primary objective was to detect factors in adipose tissue differentiating obese insulin sensitive (OBIS) from obese insulin resistant (OBIR) individuals and investigate whether adipose tissue hypoxia is a contributing factor in the pathogenesis of insulin resistance.
DESIGN AND SETTING: This was a cross sectional study in general community.
PARTICIPANTS: Subjects consisted of non-diabetic OBIS and OBIR subjects with similar BMI, age, and total body fat but different insulin sensitivity index as well as lean insulin sensitive subjects.
INTERVENTION(S): None Main Outcome Measure(s): We examined adipocytokines and the expression of candidate genes regulating hypoxia, inflammation, and lipogenesis in adipose tissue and adipose tissue oxygenation.
RESULTS: OBIS subjects had increased plasma adiponectin but similar plasma TNFα and leptin levels as compared to OBIR subjects. Genes regulating inflammation (CD68, MCP1, scavenger receptor A, and oxidized LDL receptor 1) were increased by 40-60% (p<0.05) in OBIR vs. OBIS cohorts. In addition, genes involved in extracellular matrix formation such as collagen VI and MMP7 were upregulated by 43% and 78% (p<0.05), respectively, in OBIR vs. OBIS. The expression of HIF1α and VEGF gene expression were increased by 37% and 52%, respectively, in OBIR vs. OBIS (p< 0.01). Despite the differential expression in hypoxia related genes, adipose tissue oxygenation measured by a Licox oxygen probe was not different between OBIS and OBIR subjects but it was higher in lean subjects as compared to obese subjects.
CONCLUSIONS: We confirmed that adipose tissue inflammation and fibrosis play an important role in the pathogenesis of insulin resistance independent of obesity in humans. Whether hypoxia is simply a consequence of adipose tissue expansion or is related to the pathogenesis of obesity induced insulin resistance is yet to be understood.

PMID: 26871994 [PubMed - as supplied by publisher]

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