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Cited by 440Diet and metabolism studiesDietary Effects on HealthDiet, Metabolism, and Disease

Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction

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Kirk, Erik, Reeds, Dominic N., Finck, Brian N., Mayurranjan, Mitra S., Patterson, Bruce W., Klein, Samuel·2009·Gastroenterology
DOI 10.1053/j.gastro.2009.01.048PMC PMC2677125
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Abstract

Background and Aims We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate diet or a low-carbohydrate diet on hepatic and skeletal muscle insulin sensitivity. Methods Twenty-two obese subjects (body-mass index, 36.5±0.8kg/m2) were randomized to a high-carbohydrate (>180g/d) or low-carbohydrate (<60g/d) energy-deficit diet. A euglycemic–hyperinsulinemic clamp, muscle biopsies, and magnetic resonance spectroscopy were used to determine insulin action, cellular insulin signaling and intrahepatic triglyceride content before, after 48 h, and after ~11 wks (7% weight loss) of diet therapy. Results At 48 h, intrahepatic triglyceride content decreased more in the low-carbohydrate than the high-carbohydrate diet group (29.6±4.8% vs. 8.9±1.4%; P<0.05), but was similar in both groups after 7% weight loss (low-carbohydrate diet, 38.0±4.5% vs. high-carbohydrate diet, 44.5±13.5%). Basal glucose production rate decreased more in the low-carbohydrate than the high-carbohydrate diet group at 48 h (23.4±2.2% vs. 7.2±1.4%, P<0.05) and after 7% weight loss (20.0±2.4% vs. 7.9±1.2%, P<0.05). Insulin-mediated glucose uptake did not change at 48 h, but increased similarly in both groups after 7% weight loss (48.4±14.3%, P<0.05). In both groups, insulin-stimulated phosphorylation of Jun N-terminal kinase decreased by 29±13% and phosphorylation of Akt and insulin receptor substrate -1 increased by 35±9% and 36±9%, respectively, after 7% weight loss (all p<0.05). Conclusion Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 h of calorie restriction affects the liver (intrahepatic triglyceride content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

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  • Reducing calorie intake by at least 500-1000 kcal reduces hepatic steatosis and insulin resistance.

    “Reducing calorie intake by at least 500–1000 kcal has been shown to reduce hepatic steatosis and insulin resistance [26, 27].”

    From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [27]

    The study description and Results (page unavailable) report that a 1,000 kcal/day deficit reduced intrahepatic triglyceride content and improved hepatic insulin sensitivity in obese, insulin-resistant subjects. The paper calls 500–1,000 kcal/day the recommended reduction, but its own study tested 1,000 kcal/day, not the full stated range or larger deficits. (LLM, conf=0.82)

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Authors
Kirk, E., Reeds, D. N., Finck, B. N., Mayurranjan, M. S., Patterson, B. W., & Klein, S.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Klein, Samuel
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2009-05
Volume
136
Issue
5
Pages
1552-1560
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2009.01.048
PMC
PMC2677125
OpenAlex
W2168396443
Semantic Scholar
2ea9de0f9ebdd18078c6a812581a69588b06c4a7
Cited by
440
References
47
Citations by year
2026: 12 · 2025: 18 · 2024: 18 · 2023: 37 · 2022: 23 · 2021: 32 · 2020: 27 · 2019: 26 · 2018: 22 · 2017: 31 · 2016: 22 · 2015: 18 · 2014: 32 · 2013: 30 · 2012: 28
FWCI
20.17
Type
journal article
Language
en
Update notices
erratum (2009-07-01)
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
Funders
  • National Institutes of Health (5p41rr000954-34, UL1TR000448)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK37948, DK56341, R01DK037948, P30DK056341)
  • National Center for Research Resources (P41-RR000954, RR 00954, UL1RR024992, RR.00036, M01RR000036)
  • NIH Clinical Center
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
caloric restriction, low-carbohydrate diet, high-carbohydrate diet, dietary fat, intrahepatic triglyceride, hepatic glucose production, skeletal muscle glucose uptake, insulin signaling, Akt, IRS-1, c-Jun N-terminal kinase, obesity, weight loss
MeSH terms
Adult, Blood Glucose, Body Composition, Body Weight, Dietary Carbohydrates, Dietary Fats, Female, Glucose, Homeostasis, Humans, Insulin, Insulin Resistance, Liver, Male, Obesity, Glucose Clamp Technique, Muscle, Skeletal, Caloric Restriction, Adipokines

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