Metabolic inflammation is a classic hallmark of obesity that is associated with numerous cardiometabolic complications. Disturbances in fatty acid and cholesterol metabolism are evident in obesity and likely intricately linked to the development and/or sustainment of metabolic inflammation and insulin resistance. Elevations in triglyceride-rich lipoproteins and reductions in high-density lipoprotein-cholesterol in turn are two major disturbances that accompany obesity. How metabolic dyslipidemia may contribute to metabolic inflammation is discussed. How aberrant cholesterol homeostasis coupled with excessive fatty acid accumulation prime pro-IL-1β and the evidence to support a synergistic partnership between cholesterol and fatty acids in driving metabolic inflammation are also discussed. Further, pharmaceutical and nutraceutical strategies aimed at attenuating low-grade inflammation and implications for cardiometabolic complications of obesity are reviewed. The current literature on the importance of the local tissue microenvironment in activating adipose tissue macrophages within obese adipose tissue and the contribution of these local immune cells to metabolic inflammation is reviewed. Finally, the limitations to current biomarkers of metabolic inflammation and the importance of novel sensitive biomarkers in driving obesity sub-type characterization to direct personalized medicine approaches to obesity treatment in the future are discussed.
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