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Long-term Metabolic Dysfunction Programming in Female Mice by Serial Moderate Restriction of a High-fat High-sucrose Diet. Endocrinology 2024 Aug 27;165(10)

Date

09/05/2024

Pubmed ID

39236000

Pubmed Central ID

PMC11408931

DOI

10.1210/endocr/bqae117

Scopus ID

2-s2.0-85204510410 (requires institutional sign-in at Scopus site)

Abstract

BACKGROUND: While intermittent fasting leads to weight loss and improved glucose metabolism, food insecurity, the insufficient access to food for a healthy life, is associated with obesity and adverse cardiometabolic health, especially in women. We aimed to characterize the effects of intermittently restricted feeding on energy balance and glucose tolerance in female mice.

METHODS: Female C57BL/6J mice were fed a high-fat, high-sucrose diet and intermittently food restricted to 60% of control littermates' ad libitum intake, starting at weaning and until week 19. Restricted mice were subsequently allowed ad libitum access to the same diet. Body composition and energy balance were measured at weeks 18.5, 19, 30, and 40. At week 42, mice underwent an intraperitoneal glucose tolerance test and plasma appetitive hormones measurements after nutrient gavage.

RESULTS: During the food restriction phase, restricted mice accrued lower weight and fat mass than controls despite periodic ad libitum food access. Reintroduction of continuous ad libitum food caused increased food intake during the light phase and increased body mass in restricted mice. Minor differences in body composition-adjusted energy expenditure between groups were observed at week 40. At week 42, glucose tolerance was impaired in restricted mice compared to controls, and trends toward lower levels of postprandial anorexigenic hormones glucagon-like peptide-1 and pancreatic polypeptide were observed.

CONCLUSION: Our findings suggest that repeated intermittent food restriction leads to changes in eating behavior that predispose to glucose intolerance when food is freely available. Future studies are needed to elucidate the specific mechanisms underlying these changes.

Author List

Wildes MP, Fernando DG, Grobe CC, Reho JJ, Grobe JL, Kidambi S, Kindel TL, Kwitek AE, Segar JL, Williams JS, Morselli LL

Authors

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Srividya Kidambi MD Sr Medical Director, Chief, Professor in the Medicine department at Medical College of Wisconsin
Tammy Lyn Kindel MD, PhD Associate Professor in the Surgery department at Medical College of Wisconsin
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin
Lisa Morselli MD, PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin
Joni Williams MD, MPH Director, Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Body Composition
Caloric Restriction
Diet, High-Fat
Dietary Sucrose
Energy Metabolism
Female
Glucose Intolerance
Glucose Tolerance Test
Mice
Mice, Inbred C57BL
Obesity