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Excess dietary fat rapidly induces metabolic changes, with adipose tissue responding before other organs. Data presented at the European Association for the Study of Diabetes Congress 2025 examined young volunteers who consumed either an isoenergetic diet or a high-energy, high-fat diet for three weeks.

Hyperinsulinaemic-euglycaemic clamps, tissue biopsies, and magnetic resonance spectroscopy assessed whole-body, skeletal muscle, liver, and adipose tissue metabolism. After three weeks, the high-fat diet increased body weight, fat mass index, and adipose tissue insulin resistance. Mitochondrial respiratory capacity in white adipose tissue rose significantly, while skeletal muscle insulin sensitivity, intramyocellular and hepatic lipid content, and hepatic energy metabolism remained unchanged. 

These findings indicate that white adipose tissue is the first organ to adapt to short-term overnutrition, potentially triggering whole-body insulin resistance prior to changes in muscle or liver. Understanding this early adipose tissue response could guide strategies to prevent metabolic deterioration in individuals exposed to high-energy diets.

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Key highlights
  • Short-term high-fat diet increases fat mass index and adipose tissue insulin resistance in young, glucose-tolerant individuals.
  • White adipose tissue exhibits elevated mitochondrial respiratory capacity in response to overnutrition, whereas skeletal muscle and liver metabolism remain unchanged.
  • Early metabolic adaptations in adipose tissue may initiate whole-body insulin resistance, highlighting its potential as a therapeutic target.
Source

Xourafa G, Granata C, Trenkamp S, et al. White adipose tissue adapts first: increased mitochondrial respiration and insulin resistance after short-term high-fat diet in healthy adults. Presented at: 61st EASD Annual Meeting of the European Association for the Study of Diabetes; September 15-19, 2025; Vienna, Austria. Diabetologia. 2025:241. https://link.springer.com/article/10.1007/s00125-025-06497-1#Sec43 

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White Adipose Tissue Drives Early Insulin Resistance After Short-Term High-Fat Overnutrition
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High-fat diet selectively alters adipose tissue metabolism before affecting muscle or liver

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