High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice

May 17, 2015Aging

High-fat diet causes early inflammation in fat tissue before the liver in mice

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Adipose tissue inflammation develops after 24 weeks of a high-fat diet, while hepatic inflammation appears only after 40 weeks.

C57BL/6J male mice on a high-fat diet exhibited a progressive obese phenotype and insulin resistance at 24 and 40 weeks.
Insulin resistance was reduced after 52 weeks of the high-fat diet.
Increased presence of crown-like structures and up-regulation of pro-inflammatory genes were observed in adipose tissue after 24 weeks.
Hepatic inflammation was not detected until 40 weeks of the high-fat diet.
Adipose tissue inflammation may contribute more significantly to insulin resistance than hepatic inflammation.

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Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the development of metabolic inflammation remains speculative. Thus, we aimed to elucidate the sequence of inflammatory events in adipose and hepatic tissues to determine their contribution to the development of metabolic inflammation and insulin resistance (IR) in diet-induced obesity. To confirm our hypothesis that adipose tissue (AT) inflammation is initiated prior to hepatic inflammation, C57BL/6J male mice were fed a low-fat diet (LFD; 10% kcal fat) or high-fat diet (HFD; 45% kcal fat) for either 24, 40 or 52 weeks. Lipid accumulation and inflammation was measured in AT and liver. Glucose tolerance was assessed and plasma levels of glucose, insulin, leptin and adiponectin were measured at various time points throughout the study. With HFD, C57BL/6j mice developed a progressive obese phenotype, accompanied by IR at 24 and 40 weeks of HFD, but IR was attenuated after 52 weeks of HFD. AT inflammation was present after 24 weeks of HFD, as indicated by the increased presence of crown-like structures and up-regulation of pro-inflammatory genes Tnf, Il1β, Mcp1 and F4/80. As hepatic inflammation was not detected until 40 weeks of HFD, we show that AT inflammation is established prior to the development of hepatic inflammation. Thus, AT inflammation is likely to have a greater contribution to the development of IR compared to hepatic inflammation.

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High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice

Abstract

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