IRS1 and Insulin resistance: In obese individuals, TNF-α is overexpressed in adipose tissue and activates neuronal cytokine receptors (e.g., TNF-α receptor), and this effect causes aberrant activation of stress kinases that phosphorylate insulin receptor substrate 1 (IRS-1) at serine residues, while inhibiting tyrosine phosphorylation of IRS-1, leading to insulin resistance [27,28,29].