Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 596, Issue 4, Pages 609-622Publisher
WILEY
DOI: 10.1113/JP275113
Keywords
Nutrition; Adipose tissue; Metabolism
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/H008322/1]
- European Society for Clinical Nutrition and Metabolism (ESPEN)
- Rank Prize Funds
- Arla Foods Ingredients and Kenniscentrum
- Suiker and Voeding
- Medical Research Council [MR/P002927/1]
- British Heart Foundation [PG/11/52/28989] Funding Source: researchfish
- Medical Research Council [MR/J003417/1, G9225018] Funding Source: researchfish
- BBSRC [BB/H008322/1] Funding Source: UKRI
- MRC [MR/J003417/1, G9225018, MR/P002927/1] Funding Source: UKRI
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This study assessed molecular responses of human subcutaneous abdominal adipose tissue (SCAT) to 6 weeks of morning fasting. Forty-nine healthy lean (n = 29) and obese (n = 20) adults provided SCAT biopsies before and after 6 weeks of morning fasting (FAST; 0 kcal until 12.00 h) or daily breakfast consumption (BFAST; >= 700 kcal before 11.00 h). Biopsies were analysed for mRNA levels of selected genes, and GLUT4 and Akt protein content. Basal and insulin-stimulated Akt activation and tissue glucose uptake rates were also determined. In lean individuals, lipid turnover and insulin signalling genes (ACADM and IRS2) were up-regulated with FAST versus BFAST (ACADM: 1.14 (95% CI: 0.97-1.30) versus 0.80 (95% CI: 0.64-0.96), P = 0.007; IRS2: 1.75 (95% CI: 1.33-2.16) versus 1.09 (95% CI: 0.67-1.51), P = 0.03, respectively). In obese individuals, no differential (FAST versus BFAST) expression was observed in genes involved in lipid turnover (all P > 0.1). GLUT4, Akt protein content and insulin-stimulated Akt phosphorylation were unaffected by FAST versus BFAST in both lean and obese cohorts (all P > 0.1). Lower insulin-stimulated glucose uptake rates in obese versus lean individuals were eradicated when normalised to whole-body fat mass (P = 0.416). We conclude that morning fasting up-regulates lipid turnover genes in SCAT of lean individuals. Secondly, altered SCAT insulin sensitivity with morning fasting is unlikely to be explained by signalling proximal to Akt. Finally, lower insulin-stimulated SCAT glucose uptake rates in obese individuals are proportional to whole-body fat mass, suggesting a compensatory down-regulation, presumably to prevent excessive de novo lipogenesis in adipose tissue.
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