Fat Tissue Insulin Resistance and Triglycerides.

Hypertriglyceridemia (HTG) is a known risk factor for cardiovascular diseases and is associated with insulin resistance (IR). However, the causal relationship between them remains unclear. Insulin resistance affects different tissues in various ways and may develop predominantly in muscle tissue before progressing to adipose tissues and the liver. This suggests that IR should be subdivided into tissue-specific IRs, such as muscle insulin resistance (MIR), adipose insulin resistance (AIR), and hepatic insulin resistance (HIR). HTG is believed to be particularly related to AIR.

AIR impairs glucose uptake in adipose tissues, causing elevated plasma glucose and uninhibited lipolysis. This results in a constant release of fatty acids into the bloodstream and a failure to capture fatty acids released from triglyceride-rich lipoproteins (TRLs) like very low-density lipoproteins (VLDLs) and chylomicrons. Elevated plasma fatty acids are then transported to the liver, where they contribute to the formation and secretion of VLDLs, causing an increase in plasma triglyceride levels and leading to HTG. In summary, AIR causes adipose tissues to fail in esterifying fatty acids into fats, leading to elevated plasma fatty acids, enhanced hepatic VLDL generation, and ultimately, hypertriglyceridemia.

Lee, S.J and S.W. Shin.  2023.  Tissue-specific, adipose insulin resistance leads to hypertriglyceridemia. Endocrine Abstracts (2023) 90 EP523 | DOI: 10.1530/endoabs.90.EP523.

Articles like this keep showing that one of the first metabolic changes that we see with insulin resistance and early type 2 diabetes is an increase in the TG/HDL ratio, and yet the world remains focused on LDL primarily.  This further emphasizes that in order to make a change we need to see what’s happening before a HgbA1c meets criteria for diabetes.

Jason & Rita