Table 5.

Opposing Effects of Omega-6 and Omega-3 Fatty Acids in Obesity.

Conditions	Omega-6	Omega-3
Adipogenesis (Pre-adipocyte-Adipocyte)	High AA via the PI2 receptor activates the cAMP protein kinase A, signaling pathway leads to proliferation and differentiation of WAT, prevention of its browning through inhibition of PPARy target genes including UCPI, decrease mitochondrial biogenesis [74], increasing triglycerides [73], insulin resistance, leptin resistance, decreased adiponectin levels, decreased fatty acid oxidation and hepatic steatosis [4].	High EPA and DHA partially inhibit cAMP signaling pathways triggered by AA at levels upstream of PKA [71] block COX-2 metabolites PGI2 and PGEF2a that stimulate white adipogenesis and inhibit the browning process respectively, prevent increased triglycerides and adipose tissue proliferation through UCP-I and PPARy activation, increased mitochondrial biogenesis, increased fatty acid oxidation, and apoptosis [71,75].
Inflammation	AA metabolites prostaglandin 2 thromboxane 2 and leukotriene 4 are prothrombotic and proinflammatory leading to increased production of IL-1, IL-6, NFKB and TNF and inflammation [1,64].	High dietary intake of EPA and DHA blocks the metabolites of AA and prevents inflammation, which is the hallmark of obesity [1,64,67].
Insulin Resistance Leptin Resistance Adiponectin	AA leads to insulin resistance, leptin resistance, lower adiponectin and hepatic steatosis. AA blunts PI3-Akt pathway leading to leptin resistance in the brain and deregulation of food intake [19,76,77].	EPA and DHA regulate glucose utilization, insulin sensitivity (Akt phosphorylation) in part mediated by PPARy and AMPK activation [19]. EPA and DHA regulate the secretion of adipokines involved in energy homeostasis and intermediate metabolism and in glucose and lipid metabolism. DHA restores insulin sensitivity in skeletal muscle by preventing lipotoxicity and inflammation [78,79].
Cannabinoids	AA increases the concentration of (2-AG) and (AEA) leading to excessive endocannabinoid signaling, and dysregulation of the cannabinoid system, weight gain, larger adipocytes and more macrophages in adipose tissue [80], inflammation and a metabolic profile associated with obesity [81,82].	EPA and DHA decrease 2-AG and AA in the brain while increasing DHA, decreasing the dysregulation of the cannabinoid system, improving insulin sensitivity and decreasing central body fat.