Molecular Adaptations of Adipose Tissue to 6 weeks of Morning Fasting vs Daily Breakfast Consumption in Lean and Obese Adults: Extended morning fasting and adipose tissue physiology

Javier Gonzalez, Judith Richardson, Enhad Chowdhury, Francoise Koumanov, Geoffrey Holman, Scott Cooper, Dylan Thompson, Kostas Tsintzas, James Betts

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Abstract

This experiment 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 six weeks of morning fasting (FAST; 0 kcal until 1200 h) or daily breakfast consumption (BFAST; ≥700 kcal before 1100 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 upregulated with FAST versus BFAST [1.14 (95%CI: 0.97 to 1.30) versus 0.80 (95%CI: 0.64 to 0.96), p=0.007 and 1.75 (95%CI: 1.33 to 2.16) versus 1.09 (95%CI: 0.67 to 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 upregulates 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 downregulation, presumably to prevent excessive de novo lipogenesis in adipose tissue. This trial was registered as ISRCTN31521726.
LanguageEnglish
Pages609-622
JournalJournal of Physiology
Volume596
Issue number4
Early online date28 Nov 2017
DOIs
StatusPublished - 15 Feb 2018

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Abdominal Subcutaneous Fat
Breakfast
Adipose Tissue
Fasting
Insulin
Glucose Transporter Type 4
Lipids
Glucose
Genes
Biopsy
Lipogenesis
Insulin Resistance
Up-Regulation
Down-Regulation
Phosphorylation
Messenger RNA

Keywords

  • Nutrition
  • Adipose
  • Metabolism

Cite this

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title = "Molecular Adaptations of Adipose Tissue to 6 weeks of Morning Fasting vs Daily Breakfast Consumption in Lean and Obese Adults: Extended morning fasting and adipose tissue physiology",
abstract = "This experiment 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 six weeks of morning fasting (FAST; 0 kcal until 1200 h) or daily breakfast consumption (BFAST; ≥700 kcal before 1100 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 upregulated with FAST versus BFAST [1.14 (95{\%}CI: 0.97 to 1.30) versus 0.80 (95{\%}CI: 0.64 to 0.96), p=0.007 and 1.75 (95{\%}CI: 1.33 to 2.16) versus 1.09 (95{\%}CI: 0.67 to 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 upregulates 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 downregulation, presumably to prevent excessive de novo lipogenesis in adipose tissue. This trial was registered as ISRCTN31521726.",
keywords = "Nutrition, Adipose, Metabolism",
author = "Javier Gonzalez and Judith Richardson and Enhad Chowdhury and Francoise Koumanov and Geoffrey Holman and Scott Cooper and Dylan Thompson and Kostas Tsintzas and James Betts",
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volume = "596",
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TY - JOUR

T1 - Molecular Adaptations of Adipose Tissue to 6 weeks of Morning Fasting vs Daily Breakfast Consumption in Lean and Obese Adults

T2 - Journal of Physiology

AU - Gonzalez, Javier

AU - Richardson, Judith

AU - Chowdhury, Enhad

AU - Koumanov, Francoise

AU - Holman, Geoffrey

AU - Cooper, Scott

AU - Thompson, Dylan

AU - Tsintzas, Kostas

AU - Betts, James

PY - 2018/2/15

Y1 - 2018/2/15

N2 - This experiment 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 six weeks of morning fasting (FAST; 0 kcal until 1200 h) or daily breakfast consumption (BFAST; ≥700 kcal before 1100 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 upregulated with FAST versus BFAST [1.14 (95%CI: 0.97 to 1.30) versus 0.80 (95%CI: 0.64 to 0.96), p=0.007 and 1.75 (95%CI: 1.33 to 2.16) versus 1.09 (95%CI: 0.67 to 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 upregulates 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 downregulation, presumably to prevent excessive de novo lipogenesis in adipose tissue. This trial was registered as ISRCTN31521726.

AB - This experiment 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 six weeks of morning fasting (FAST; 0 kcal until 1200 h) or daily breakfast consumption (BFAST; ≥700 kcal before 1100 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 upregulated with FAST versus BFAST [1.14 (95%CI: 0.97 to 1.30) versus 0.80 (95%CI: 0.64 to 0.96), p=0.007 and 1.75 (95%CI: 1.33 to 2.16) versus 1.09 (95%CI: 0.67 to 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 upregulates 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 downregulation, presumably to prevent excessive de novo lipogenesis in adipose tissue. This trial was registered as ISRCTN31521726.

KW - Nutrition

KW - Adipose

KW - Metabolism

U2 - 10.1113/JP275113

DO - 10.1113/JP275113

M3 - Article

VL - 596

SP - 609

EP - 622

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 4

ER -