Abstract

Preadipocytes contribute to the inflammatory responses within adipose tissue. Whilst fatty acids are known to elicit an inflammatory response within adipose tissue, the relative contribution of preadipocytes and mature adipocytes to this is yet to be determined. We aimed to examine the actions of common dietary fatty acids on the acute inflammatory and adipokine response in 3T3-L1 preadipocytes and differentiated mature adipocytes. Gene expression levels of key adipokines in 3T3-L1 preadipocytes and adipocytes were determined following incubation with palmitic acid, myristic acid or oleic acid and positive inflammatory control, lipopolysaccharide for 2 and 4 h. Inflammatory kinase signalling was assessed by analysis of nuclear factor-κB, p38-mitogen-activated protein kinase and c-jun amino-terminal kinase phosphorylation. Under basal conditions, intracellular monocyte chemoattractant protein-1 and interleukin-6 gene expression levels were increased in preadipocytes, whereas mature adipocytes expressed increased gene expression levels of leptin and adiponectin. Fatty acid exposure at 2 and 4 h increased both monocyte chemoattractant protein-1 and interleukin-6 gene expression levels in preadipocytes to greater levels than in mature adipocytes. There was an accompanying increase of inhibitor of κB-α degradation and nuclear factor-κB (p65) (Ser536) phosphorylation with fatty acid exposure in the preadipocytes only. The current study points to preadipocytes rather than the adipocytes as the contributors to both immune cell recruitment and inflammatory adipokine secretion with acute increases in fatty acids.

Highlights

  • Adipose tissue is broadly comprised of two fractions, mature adipocytes and the stromal vascular fraction (SVF) [1,2,3,4], where the latter generates many of the pro-inflammatory factors secreted from adipose tissue [1]

  • The propensity for greater inflammatory response in preadipocytes is mediated by the nuclear factor-kB (NF-kB) and mitogen-activated protein kinases (MAPK) such as c-jun amino-terminal kinase (JNK) signalling in preadipocyte cells compared with mature adipocytes [9]

  • Intracellular MCP-1 and IL-6 gene expression levels were increased in preadipocytes compared with mature adipocytes before and after fatty acid (FA) exposure

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Summary

Introduction

Adipose tissue is broadly comprised of two fractions, mature adipocytes and the stromal vascular fraction (SVF) [1,2,3,4], where the latter generates many of the pro-inflammatory factors secreted from adipose tissue [1]. Cytokine secretion from adipose tissue is acutely influenced by the macronutrient composition of a meal and further by the lipid species present within high-fat meals [10]. Dysregulation of acute metabolic adaptations occur in people with chronic metabolic disorders. Inflammatory markers such as TNFa, IL-6 and ICAM-1 are increased in healthy individuals, but are reported to be higher in T2D patients after 4 hours following a high fat meal [11]. Following the consumption of high saturated fatty acid (SFA), monounsaturated fatty acid (MUFA) or polyunsaturated fatty acid (PUFA) milkshakes, overweight and obese adults exhibit increased plasma CRP levels for up to 6 hours, with no difference between FA composition of the beverage, whereas TNFa and VCAM levels remain stable. ICAM levels were observed to be reduced following consumption of the MUFA meal compared with SFA and PUFA meals, indicating the importance of the FA composition in postprandial regulation of inflammation [12]

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