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During the initial hours of fasting, the body uses up its glycogen stores as an energy source. Once these glycogen reserves are depleted, the body begins breaking down stored triglycerides and structural proteins. During this stage, glycerol becomes a key substrate for gluconeogenesis, while free fatty acids undergo beta-oxidation to provide energy for tissues, such as skeletal muscle. In the fasting state, the body spares protein breakdown as much as possible to conserve muscle and structural...
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Related Experiment Video

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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
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A Very-low-energy Fast Involves Increased Adipose Inflammatory Gene Expression: A 6-day Feeding Trial (FASTOMICS-6).

Marianne Bråtveit1,2, Pouda P Strømland2, Johnny Laupsa-Borge1,3

  • 1Centre for Nutrition, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway.

The Journal of Clinical Endocrinology and Metabolism
|October 28, 2025
PubMed
Summary

A 6-day very-low energy fast significantly altered metabolism in obese patients, increasing ketone bodies and inflammation while improving insulin sensitivity. This suggests inflammatory and autophagy pathways are key to adapting to fasting.

Keywords:
adipose tissuecalorie restrictionfastinggene expressionmetabolomicsobesity

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Area of Science:

  • Metabolic studies
  • Human physiology
  • Nutritional science

Background:

  • Fasting and ketogenic diets offer potential health benefits.
  • Human tissue mechanisms and metabolome changes during fasting require further investigation.

Purpose of the Study:

  • To investigate changes in subcutaneous adipose tissue (SAT) gene expression, plasma metabolomics, and serum markers following a 6-day very-low-energy fast.
  • To understand the molecular and metabolic adaptations to short-term fasting in individuals with obesity.

Main Methods:

  • 13 patients with obesity (BMI 41.6) participated in a 6-day, 600 kcal/day feeding study.
  • Body composition, blood, and SAT were analyzed for metabolomics and transcriptomics before and after the fast.
  • Gene Set Enrichment Analysis (GSEA) and Weighted Gene Correlation Network Analysis (WGCNA) were used to infer biological pathways.

Main Results:

  • Significant reductions in fat mass (-2.07%) and fat-free mass (-4.42%) were observed.
  • Marked increases in ketone bodies (+615%) and α-hydroxybutyrate (+103%) occurred.
  • Decreases in fasting insulin (-41.2%), HOMA2-IR (-31.8%), and advanced glycation end-products (AGEs) like Carboxyethyl-Lysine (-46.0%) and Carboxymethyl-Lysine (-50.9%) were noted.
  • SAT showed upregulated inflammatory responses and downregulated oxidative phosphorylation, adipogenesis, fatty acid metabolism, and mTORC1 signaling.

Conclusions:

  • A 6-day very-low energy fast increased adipose inflammatory gene expression.
  • Plasma AGEs decreased, and insulin sensitivity improved.
  • These findings suggest a role for inflammatory and autophagy-associated pathways in metabolic adaptation to ketogenic fasting.