Abstract
ObjectiveThe enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death.Experimental ApproachObesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice.ResultsCompared to WT mice, CD36 KO mice fed a high fat diet exhibited reduced adiposity and adipose tissue inflammation, with decreased adipocyte cell death, pro-inflammatory cytokine expression and macrophage and T-cell accumulation. In primary cell culture, the absence of CD36 expression in macrophages decreased pro-inflammatory cytokine, pro-apoptotic and ER stress gene expression in response to lipopolysaccharide (LPS). Likewise, CD36 deficiency in primary adipocytes reduced pro-inflammatory cytokine and chemokine secretion in response to LPS. Primary macrophage and adipocyte co-culture experiments showed that these cell types act synergistically in their inflammatory response to LPS and that CD36 modulates such synergistic effects.ConclusionsCD36 enhances adipose tissue inflammation and cell death in diet-induced obesity through its expression in both macrophages and adipocytes.
Highlights
Obesity, especially visceral obesity, is a well-described risk factor for the development of atherosclerotic cardiovascular disease, type II diabetes mellitus and fatty liver disease [1]
Obesity and Adipose Tissue Inflammation CD36 KO mice were found to be leaner than control (WT)
In agreement with the recent studies [29], [30], we found that epididymal fat from wild type (WT) mice on a HFD showed significant F4/80-positive macrophage accumulation and increased numbers of crown-like structures which are associated with necrotic adipocytes (Fig. 2A, 2B, 2D)
Summary
Especially visceral obesity, is a well-described risk factor for the development of atherosclerotic cardiovascular disease, type II diabetes mellitus and fatty liver disease [1]. Alterations in lipid metabolism and the development of ER stress contribute to the activation of stress signaling pathways, such as the JNK and NFkB cascades [4], [5]. Pro-inflammatory chemokines and cytokines are released and macrophages are recruited into WAT. In obese WAT, moribund adipocytes are surrounded by macrophages in ‘‘crown-like’’ structures (CLS) [6], [7], [8]. Such activated macrophages release additional pro-inflammatory cytokines, such as TNFa and IL-1b, which cause further adipocyte death and stress signaling [3], [9]. The initiation steps in adipocyte stress and death remain poorly defined
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