Lipid Metabolism and Insulin Sensitivity Mechanisms

Lipid metabolism encompasses the synthesis, transport and breakdown of fatty acids and triglycerides across key tissues such as liver, adipose and skeletal muscle. In the post-prandial state, de novo lipogenesis in hepatocytes and adipocytes converts excess carbohydrates into fatty acids, which are then esterified into triglycerides for storage or secreted in very low-density lipoproteins. During fasting or increased energy demand, hormonal cues—most notably a decline in insulin and rise in catecholamines—trigger adipose lipolysis and hepatic fatty acid oxidation to supply tissues with energy substrates. Insulin sensitivity refers to the ability of insulin to promote glucose uptake in muscle and adipose and to suppress hepatic gluconeogenesis. Dysregulation of lipid flux, accumulation of bioactive lipid intermediates (for example diacylglycerols and ceramides) and ectopic fat deposition in liver and muscle are central drivers of insulin resistance. Chronic overnutrition and obesity shift the balance towards lipid oversupply, provoke low-grade inflammation in adipose depots and impair insulin signal transduction, thereby establishing a vicious cycle of hyperinsulinaemia, further lipogenesis and metabolic dysfunction. Understanding the molecular links between lipid handling and insulin action has broad implications for the prevention and treatment of type 2 diabetes, non-alcoholic fatty liver disease and related cardiometabolic disorders.

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Lipid Metabolism and Insulin Sensitivity Mechanisms publication trend

The graph below shows the total number of articles in lipid metabolism and insulin sensitivity mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Stearoyl-CoA desaturase 1 (SCD1): An enzyme that introduces a cis double bond into saturated fatty acyl-CoAs, producing monounsaturated fatty acids essential for triglyceride and membrane lipid synthesis.

De novo lipogenesis (DNL): The metabolic conversion of acetyl-CoA into fatty acids, primarily occurring in liver and adipose tissue under carbohydrate-rich conditions.

Insulin sensitivity: The capacity of target cells to respond effectively to insulin by promoting glucose uptake and modulating lipid metabolism.

Hepatic steatosis: Excessive accumulation of triglycerides within hepatocytes, commonly referred to as fatty liver.

Lipotoxicity: Adverse cellular effects resulting from the buildup of lipid intermediates such as diacylglycerols and ceramides that impair signalling and viability.

References

1. Identification of novel SCD1 inhibitor alleviates nonalcoholic fatty liver disease: critical role of liver-adipose axis. Cell Communication and Signaling (2023).
2. 6-Gingerol Inhibits De Novo Lipogenesis by Targeting Stearoyl-CoA Desaturase to Alleviate Fructose-Induced Hepatic Steatosis. International Journal of Molecular Sciences (2024).
3. New advances in drug development for metabolic dysfunction-associated diseases and alcohol-associated liver disease. Cell & Bioscience (2024).