Abstract
BackgroundThe acute phase response (APR) is characterized by alterations in lipid and glucose metabolism leading to an increased delivery of energy substrates. In adipocytes, there is a coordinated decrease in Free Fatty acids (FFAs) and glucose storage, in addition to an increase in FFAs mobilization. Serum Amyloid A (SAA) is an acute phase protein mainly associated with High Density Lipoproteins (HDL). We hypothesized that enrichment of HDL with SAA, during the APR, could be implicated in the metabolic changes occurring in adipocytes.Methodology/Principal Findings In vitro differentiated human adipocytes (hMADS) were treated with SAA enriched HDL or recombinant SAA and the metabolic phenotype of the cells analyzed. In hMADS, SAA induces an increased lipolysis through an ERK dependent pathway. At the molecular level, SAA represses PPARγ2, C/EBPα and SREBP-1c gene expression, three transcription factors involved in adipocyte differentiation or lipid synthesis. In addition, the activation of the NF-κB pathway by SAA leads to the induction of pro-inflammatory cytokines and chemokines, as in the case of immune cells. These latter findings were replicated in freshly isolated mature human adipocytes.Conclusions/SignificanceBesides its well-characterized role in cholesterol metabolism, SAA has direct metabolic effects on human adipocytes. These metabolic changes could be at least partly responsible for alterations of adipocyte metabolism observed during the APR as well as during pathophysiological conditions such as obesity and conditions leading to insulin resistant states.
Highlights
The acute phase response (APR) induced during infection or inflammation, is an early and highly complex reaction of the host, which protects it from further injury
Serum Amyloid A (SAA) and saaHDL stimulate lipolysis As already shown in human and porcine adipocytes, we found that SAA and SAA-enriched High Density Lipoproteins (HDL) were able to stimulate lipolysis by a mechanism involving the phosphorylation of hormone sensitive lipase (HSL)
We examined the effects of both SAA and saaHDL on cytokine and chemokine secretion in human adipocytes (hMADS) adipocytes following a 24 h treatment
Summary
The acute phase response (APR) induced during infection or inflammation, is an early and highly complex reaction of the host, which protects it from further injury. Liver and adipose tissue ensures a high flow of glucose and Free Fatty Acids (FFAs) to the predominantly energy-consuming cells, such as the inflammatory and immune cells [4]. The hepatic-linked hyperglycemia and hypertriglyceridemia produced throughout the APR could be a consequence of alterations of adipose tissue metabolism [5]. In adipocytes, there is a coordinated decrease in FFA storage and an increase in glycerol and FFA mobilization through stimulation of lipolysis, which could potentially affect hepatic metabolism [1]. The acute phase response (APR) is characterized by alterations in lipid and glucose metabolism leading to an increased delivery of energy substrates. There is a coordinated decrease in Free Fatty acids (FFAs) and glucose storage, in addition to an increase in FFAs mobilization. We hypothesized that enrichment of HDL with SAA, during the APR, could be implicated in the metabolic changes occurring in adipocytes
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