Insulin Resistance

Metabolic Effects of Obesity and Its Interaction with Endocrine Diseases

“…11,12 resistance are classically assessed by the euglycemic-hyperinsulinemic clamp (EHC), in which insulin is infused at a variable rate to keep blood glucose within a set of predetermined parameters. The infusion rate necessary to accomplish this is an indicator of the response of peripheral tissues to insulin, that is, the less insulin necessary to control blood glucose, the more insulin-sensitive the individual.…”

“…However, this is an active area of study in human medicine, and potential mechanisms include: Cellular hypoxia resulting from adipocyte hypertrophy, which leads to oxidative stress, apoptosis, and an inflammatory response that negatively impacts fuel metabolism 8,9 ; Decreased adipocyte mitochondrial function, independent of cell size 10 ; Altered secretion of adipokines and other bioactive substances, including those involved in insulin sensitivity and inflammation 6 ; and Abnormal fatty acid trafficking that results in increased delivery of lipids to lean tissue and intracellular accumulation of lipid intermediates (eg, fatty acyl coenzyme A, ceramides, and diacylglycerol) that interfere with insulin signaling. 11,12 Therefore, at least in humans and rodents, it seems that increased fat mass results in a reduced ability of adipose tissue to perform its usual metabolic roles, beginning at a molecular level and culminating in systemic consequences. The effects of obesity on adipose tissue have been referred to as "adiposopathy" or "adipose tissue dysfunction" by some investigators (Box 1).…”

Distinct metabolic phenotypes towards cardiometabolic diseases

“…The endogenously-derived verylow density lipoprotein (VLDL)-TAG and exogenously-derived chylomicron-TAG are hydrolyzed by LPL to facilitate plasma FFA clearance by adipocytes (39,40). In insulin resistant and obese states, LPL activity is reduced, resulting in reduced TAG clearance by adipose tissue (40)(41)(42). Additionally, adipose tissue of individuals with obesity is characterized by decreased adipose tissue blood flow and angiogenesis, increased tissue fibrosis, increased inflammation, and a lower capacity to recruit adipocyte precursor cells, thereby limiting the ability to expand through hyperplasia (42)(43)(44).…”

“…In insulin resistant and obese states, LPL activity is reduced, resulting in reduced TAG clearance by adipose tissue (40)(41)(42). Additionally, adipose tissue of individuals with obesity is characterized by decreased adipose tissue blood flow and angiogenesis, increased tissue fibrosis, increased inflammation, and a lower capacity to recruit adipocyte precursor cells, thereby limiting the ability to expand through hyperplasia (42)(43)(44). Together, dysfunctional hypertrophic adipocytes in obesity show a lower storage capacity for lipids compared to adipocytes in individuals of normal weight (26,44).…”

“…Together, dysfunctional hypertrophic adipocytes in obesity show a lower storage capacity for lipids compared to adipocytes in individuals of normal weight (26,44). Decreased lipid storage capacity leads to a reduced TAG clearance, and thus increased TAG and FFA spillover, resulting in increased lipid supply to other organs, thus contributing to ectopic fat deposition and insulin resistance (41,42).…”