Metabolic Effects of High-Fat Diets on Insulin Sensitivity
Summary
High-fat dietary patterns are implicated in the pathogenesis of insulin resistance through multiple convergent mechanisms. Excess dietary lipids promote ectopic fat accumulation within skeletal muscle, liver and pancreatic islets, provoking lipotoxic alterations in mitochondrial function and eliciting a pro-inflammatory milieu within adipose tissue. Such changes interrupt insulin receptor signal transduction and impair the mobilisation of glucose transporters to the cell surface, diminishing glucose uptake efficiency. At the whole-body level, high-fat feeding shifts substrate utilisation away from glucose towards fatty acid oxidation, thereby sustaining hyperglycaemia and compensatory hyperinsulinaemia. Emerging investigations also implicate gut microbiota perturbations and bile acid metabolism in modulating insulin sensitivity in response to lipid-rich diets. These insights have direct relevance to the global rise in type 2 diabetes and inform nutritional and pharmacological strategies aimed at restoring metabolic flexibility and preserving insulin action.
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Metabolic Effects of High-Fat Diets on Insulin Sensitivity publication trend
The graph below shows the total number of articles in metabolic effects of high-fat diets on insulin sensitivity across all publications each year (not limited to Nature Index journals).
Technical terms
Insulin sensitivity: The efficiency with which target tissues increase glucose uptake in response to circulating insulin.
GLUT4 translocation: The process by which insulin stimulates movement of the GLUT4 glucose transporter from intracellular vesicles to the cell membrane.
Ectopic lipid deposition: Accumulation of triglycerides in non-adipose tissues such as muscle and liver, impairing normal cellular functions.
Acyl-CoA synthetase: An enzyme that activates long-chain fatty acids by conjugating them with coenzyme A, facilitating their metabolism and incorporation into lipid intermediates.
Gluconeogenesis: The metabolic pathway generating glucose from non-carbohydrate substrates, including glycerol and amino acids, primarily in the liver.
References
- A High Fat Diet Impairs Stimulation of Glucose Transport in Muscle FUNCTIONAL EVALUATION OF POTENTIAL MECHANISMS*. Journal of Biological Chemistry (1998).
- [U-14C]glucose metabolism in vivo in rats rendered obese by a high fat diet. Journal of Lipid Research (1975).
- Association of Acyl-CoA Synthetase-1 with GLUT4-containing Vesicles*. Journal of Biological Chemistry (1998).
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