TNF-α and adipocyte biology

Abstract 

Dyslipidemia and insulin resistance are commonly associated with catabolic or lipodystrophic conditions (such as cancer and sepsis) and with pathological states of nutritional overload (such as obesity-related type 2 diabetes). Two common features of these metabolic disorders are adipose tissue dysfunction and elevated levels of tumour necrosis factor-alpha (TNF-α). Herein, we review the multiple actions of this pro-inflammatory adipokine on adipose tissue biology. These include inhibition of carbohydrate metabolism, lipogenesis, adipogenesis and thermogenesis and stimulation of lipolysis. TNF-α can also impact the endocrine functions of adipose tissue. Taken together, TNF-α contributes to metabolic dysregulation by impairing both adipose tissue function and its ability to store excess fuel. The molecular mechanisms that underlie these actions are discussed.

Abbreviations: TNF-α, tumour necrosis factor-alpha, sTNF-α, soluble tumour necrosis factor-alpha, mTNF-α, transmembrane tumour necrosis factor-alpha, T2D, type 2 diabetes, TNFR1, tumour necrosis factor-alpha receptor 1, TNFR2, tumour necrosis factor-alpha receptor 2, WAT, white adipose tissue, BAT, brown adipose tissue, PPARγ, peroxisome proliferator-activated receptor gamma, C/EBPα, CCAAT/enhancer binding protein, LPL, lipoprotein lipase, HSL, hormone sensitive lipase, NFκB, nuclear factor-kappa B, IκB, inhibitor of NFκB, IKKβ, IκB kinase beta, JNK, c-jun N-terminal kinase, ERK1/2, extracellular signal-regulated kinase, AMPK, AMP-activated protein kinase

Keywords: Obesity, Type 2 diabetes, Metabolic syndrome, Insulin resistance, Dyslipidemia, TNF signalling, Lipid metabolism, Antiadipogenesis