Over the past decade the prevalence of obesity in Kuwait, and worldwide, has increased at an epidemic proportion. It is estimated that 42% of the Kuwaiti population is obese, while 52.5% are considered overweight (1, 2). It is well documented that obesity occurs due to the excessive consumption of a diet high in saturated fat, and that it is correlated with both chronic inflammation and deranged cellular metabolism. All of which are believed to be risk factors of insulin resistance syndrome (3, 4). 

	Tumour necrosis factor (TNF)-alpha is a key protein that is secreted by adipose tissue, which is found in excess levels  in both obese humans and animals, its expression leads to the activation of pro-inflammatory pathways known to influence insulin sensitivity(5). At gene level, TNF-α acts as a local signal regulator that induces fatty acid lipolysis in an organ specific manner. This in turn leads to increased accumulation of intercellular fatty acids (FA) and ultimately lipotoxicity (6).  This effect was further documented in obese patient sera, where excess TNF-a expression in sera was found to influence the behaviour of monocytes leading to lipid laden  monocytic cells. The higher FA content within the monocyte the more it aggravates their inflammatory phenotype favoring pro-inflammatory macrophages (M1) that secrete high levels of pro-inflammatory cytokines such as IL-1β, IL-6 IL-8 and TNF-α(7). This process of up-regulation of TNF-a creates a vicious cycle of inflammation and insulin resistance that correlates with the pathology of Type 2 Diabetes (T2D) (3, 8). 
	
	It is still unclear how functional changes within the monocytic lipid metabolites are essential to the monocyte/macrophage inflammatory response, and how it influences the phenotypic switch over the course of obesity-related inflammation. Therefore, in this current study, we aim to investigate the potential link between the inhibition of different lipid metabolites and inflammatory responses in TNF-a stimulated monocyte/macrophage cultures.

TNF-alpha modulates macrophage polarization to M1 phenotype via lipid metabolism