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Current Pharmaceutical Design
ISSN (Print): 1381-6128
ISSN (Online): 1873-4286
VOLUME: 14
ISSUE: 12
DOI: 10.2174/138161208784246153      Price:  $58









Adipose Tissue Macrophages, Low Grade Inflammation and Insulin Resistance in Human Obesity

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Author(s): Leonie K. Heilbronn and Lesley V. Campbell
Pages 1225-1230 (6)
Abstract:
Obesity was first described as a low-grade inflammatory condition more than a decade ago. However, it is only relatively recently that obese individuals have been described with increased macrophage infiltration of adipose tissue, as well as an increase in the number of “M1” or “classically activated” macrophages. Furthermore, macrophages have been identified as the primary source of many of the circulating inflammatory molecules that are detected in the obese state and are postulated to be causal both in the development of insulin resistance and in the progression to type 2 diabetes. There is also novel evidence to suggest that macrophages inhibit adipocyte differentiation, potentially leading to adipocyte hypertrophy, altered secretion of adipokines and ectopic storage of lipid within liver, muscle and other non-adipose tissues. Currently, it is not clear what causes increased macrophage infiltration of adipose tissue in obese individuals. Theories include altered signalling by adipocytes, nutritional induction of metabolic endotoxemia or reduced angiogenesis and local adipose cell hypoxia. Importantly, PPAR-gamma agonists have been shown to alter macrophage phenotype to “M2” or an “alternatively activated” anti-inflammatory phenotype and may induce macrophage specific cell death. Consequently, excitement surrounds the potential for specific inhibition of macrophage infiltration of adipose tissue via pharmacotherapy for obese patients and more particularly as adjunct therapy to improve insulin sensitivity in obese individuals with insulin resistance and overt type 2 diabetes.
Keywords:
Obesity, insulin resistance, inflammation, adipose tissue macrophages, type 2 diabetes
Affiliation:
Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst NSW 2010, Australia.