Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults
Open accessAbstract
Caloric restriction (CR) improves insulin sensitivity and reduces the incidence of diabetes in obese individuals. The underlying mechanisms whereby CR improves insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 obese participants (BMI = 35 kg/m(2)) compared with 9 matched control subjects (BMI = 34 kg/m(2)). Compared with the control subjects, CR increased the glucose infusion rate needed to maintain euglycemia during hyperinsulinemia, indicating enhancement of peripheral insulin sensitivity. This improvement in insulin sensitivity was not accompanied by changes in skeletal muscle mitochondrial oxidative capacity or oxidant emissions, nor were there changes in skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels. However, CR lowered insulin-stimulated thioredoxin-interacting protein (TXNIP) levels and enhanced nonoxidative glucose disposal. These results support a role for TXNIP in mediating the improvement in peripheral insulin sensitivity after CR.
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Weight loss by caloric restriction in obese people enhances insulin sensitivity but does not improve maximal mitochondrial oxidative capacity in isolated mitochondria or mitochondrial content.
“Weight loss by caloric restriction in obese people enhanced insulin sensitivity but did not improve maximal mitochondrial oxidative capacity in isolated mitochondria or mitochondrial content (91,92).”
From Altered mitochondrial function in insulin-deficient and insulin-resistant states (2018) · cites this paper as [91]
Caloric restriction designed to reduce body weight by 10% within 16 weeks in obese humans can significantly improve insulin sensitivity even without improvements in mitochondrial content and oxidative capacity.
“Two separate studies have shown that even in the absence of improvements in mitochondrial content and oxidative capacity, CR designed to reduce body weight by 10% within 16 weeks in obese humans can significantly improve insulin sensitivity.116, 117”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [116]
In 11 obese individuals, 16 weeks of CR increased insulin sensitivity but did not affect skeletal muscle mitochondrial oxidative capacity or oxidant emissions.
“Similarly, 16 weeks of CR increased insulin sensitivity in 11 individuals who were obese but did not affect skeletal muscle mitochondrial oxidative capacity or oxidant emissions (Johnson et al., 2016).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Johnson et al., 2016
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- Authors
- Johnson, M. L., Distelmaier, K., Lanza, I. R., Irving, B. A., Robinson, M. M., Konopka, A. R., Shulman, G. I., & Nair, K. S.
- Affiliations
- Mayo Clinic (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Nair, K. Sreekumaran
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2015-08-31
- Volume
- 65
- Issue
- 1
- Pages
- 74-84
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC4686951
- OpenAlex
- W2210293160
- Cited by
- 129
- References
- 54
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 17 · 2023: 8 · 2022: 11 · 2021: 12 · 2020: 14 · 2019: 14 · 2018: 17 · 2017: 10 · 2016: 5 · 2015: 2
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U24-DK-100469, DK-50456, T32-DK-007198, T32-DK-007352, R01-DK-49230, R24-DK-090963, R01-DK-41973, UL1-TR-000135)
- National Center for Advancing Translational Sciences (KL2-TR-000136-07, KL2-RR-024151)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- caloric restriction, insulin sensitivity, obesity, sedentary adults, TXNIP, nonoxidative glucose disposal, skeletal muscle, mitochondrial oxidative capacity, ceramide, diacylglycerol, hyperinsulinemic-euglycemic clamp, type 2 diabetes prevention
- MeSH terms
- Amino Acids, Blood Glucose, Calorimetry, Indirect, Carrier Proteins, Ceramides, Diglycerides, Energy Metabolism, Female, Humans, Hydrogen Peroxide, Insulin Resistance, Male, Middle Aged, Mitochondria, Muscle, Obesity, Oxidation-Reduction, Blotting, Western, Glucose Clamp Technique, Case-Control Studies, Muscle, Skeletal, Caloric Restriction, Sedentary Behavior
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