Chronic exposure to palmitic acid-induced adipocyte hypertrophy and altered batokine gene expression in T37i brown adipocytes

Abstract

Enlargement of adipose tissue through hypertrophy is a key hallmark of obesity. Our previous study demonstrated that chronic obesity induces brown adipose tissue hypertrophy and altered batokine gene expression patterns in vivo. The present study further explored and verified the pathophysiological and molecular changes implicated in brown adipocyte hypertrophy by exposing T37i cells to 0.25, 0.5, 0.75, and 1 mM of palmitic acid for 48 h. The results showed that palmitic acid-induced intracellular lipid accumulation and lipolysis. Gene expression analysis demonstrated that palmitic acid downregulated genes responsible for glucose and lipid metabolism, such as AdipoQ and PIk3r1, while upregulating Cpt1A, a mitochondrial fatty acid transporter, and Tnf-α, a pro-inflammatory cytokine. Moreover, palmitic acid downregulated brown adipocyte transcriptional factors and thermogenic markers, including Prdm16, Pparg, Cidea, Dio2, Sirt1, and Ucp1. Gene expression of batokines involved in regulating substrate metabolism (Fgf21), angiogenesis (Nrg4 and VegfA), and immune cell recruitment (Metrnl, Gdf15, and Cxcl14) were altered by palmitic acid. This data has demonstrated that palmitic acid contributes to the hypertrophy and whitening of brown adipocytes by inhibiting brown adipocyte differentiation and altering batokines expression patterns.