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

Abstract

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.

Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice

“…A recent study reported that increased hepatic CD36 expression with age is associated with enhanced hepatic fat uptake and increased susceptibility to NAFLD (Sheedfar et al 2014). Meanwhile, in another study, HFD-induced obesity primes inflammation in adipose tissue prior to development of hepatic inflammation (van der Heijden et al 2015a). Aging is associated with increased visceral adiposity linked to adipose tissue inflammation and systemic increase in pro-inflammatory cytokines.…”

“…Although there has been limited data available regarding the differential effect of HFD feeding on the progression of NAFLD and/or renal injury, a few papers have been published on these topics recently (Sheedfar et al 2014;van der Heijden et al 2015a). A recent study reported that increased hepatic CD36 expression with age is associated with enhanced hepatic fat uptake and increased susceptibility to NAFLD (Sheedfar et al 2014).…”

Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

“…Metabolic complications in adipose tissue generally precede similar complications in other tissues, such as the liver [38,39]. TNFα produced in adipose tissue may migrate into the circulation and exert pro-inflammatory effects on other tissues [38,39].…”

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

“…In Study 1, development of insulin resistance and glucose intolerance in HFD-fed mice was confirmed by insulin and glucose tolerance tests at 24 weeks (data not shown). Study 3 showed that this insulin sensitivity was attenuated upon prolonged HFD feeding, as the HFD group initially showed a similar increase in insulin levels but then recuperation to LFD-fed control levels as of week 40 17 . Also, HFDfed mice steadily increased their body weight during the first 40 weeks, after which body weight stabilised until the end of the study.…”