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Publication
A major role of insulin in promoting obesity-associated adipose tissue
inflammation.
Authors Pedersen DJ, Guilherme A, Danai LV, Heyda L, Matevossian A, Cohen J, Nicoloro
SM, Straubhaar J, Noh HL, Jung D, Kim JK, Czech MP
Submitted By Submitted Externally on 10/1/2015
Status Published
Journal Molecular metabolism
Year 2015
Date Published 7/1/2015
Volume : Pages 4 : 507 - 18
PubMed Reference 26137438
Abstract Adipose tissue (AT) inflammation is associated with systemic insulin resistance
and hyperinsulinemia in obese rodents and humans. A longstanding concept is that
hyperinsulinemia may promote systemic insulin resistance through downregulation
of its receptor on target tissues. Here we tested the novel hypothesis that
insulin also impairs systemic insulin sensitivity by specifically enhancing
adipose inflammation., Circulating insulin levels were reduced by about 50% in
diet-induced and genetically obese mice by treatments with diazoxide or
streptozotocin, respectively. We then examined AT crown-like structures,
macrophage markers and pro-inflammatory cytokine expression in AT. AT
lipogenesis and systemic insulin sensitivity was also monitored. Conversely,
insulin was infused into lean mice to determine its affects on the above
parameters., Lowering circulating insulin levels in obese mice by streptozotocin
treatment decreased macrophage content in AT, enhancing insulin stimulated Akt
phosphorylation and de novo lipogenesis (DNL). Moreover, responsiveness of blood
glucose levels to injected insulin was improved by streptozotocin and diazoxide
treatments of obese mice without changes in body weight. Remarkably, even in
lean mice, infusion of insulin under constant euglycemic conditions stimulated
expression of cytokines in AT. Consistent with these findings, insulin treatment
of 3T3-L1 adipocytes caused a 10-fold increase in CCL2 mRNA levels within 6 h,
which was blocked by the ERK inhibitor PD98059., Taken together, these results
indicate that obesity-associated hyperinsulinemia unexpectedly drives AT
inflammation in obese mice, which in turn contributes to factors that suppress
insulin-stimulated adipocyte DNL and systemic insulin sensitivity.




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