Supplemental Berberine in a High-Fat Diet Reduces Adiposity and Cardiac Dysfunction in Offspring of Mouse Dams with Gestational Diabetes Mellitus
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Abstract
Background There are few evidence-based strategies to attenuate the risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties. Objectives We hypothesized that dietary BBR would improve health outcomes in the mouse offspring of GDM dams. Methods Wild-type C57BL/6 female mice were fed either a Lean-inducing low-fat diet (L-LF,10% kcal fat, 35% kcal sucrose) or a GDM-inducing high-fat diet (GDM-HF, 45% kcal fat, 17.5% sucrose) for 6 wk prior to breeding with wild-type C57BL/6 male mice throughout pregnancy and the suckling period. The resulting Lean and GDM-exposed male and female offspring were randomly assigned an LF (10% kcal fat, 35% kcal sucrose), HF (45% kcal fat, 17.5% sucrose), or high-fat berberine (HFB) (45% kcal fat, 17.5% sucrose diet) containing BBR (160 mg/kg/d, HFB) at weaning for 12 wk. The main outcome was to evaluate the effects of BBR on obesity, pancreatic islet function, and cardiac contractility in GDM-exposed HF-fed offspring. Significance between measurements was determined using a 2 (gestational exposure) × 3 (diet) factorial design by a 2- way ANOVA using Tukey post-hoc analysis. Results In the GDM-HF group, body weights were significantly increased (16%) compared with those in baseline (L-LF) animals (P < 0.05). Compared with the L-LF animals, the GDM-HF group had a reduction in pancreatic insulin glucose-stimulated insulin secretion (74%) and increased cardiac isovolumetric contraction time (IVCT; ∼150%) (P < 0.05). Compared with GDM-HF animals, the GDM-HFB group with the dietary addition of BBR had significantly reduced body weight (16%), increased glucose-stimulated insulin secretion from pancreatic islets (254%), and reduced systolic heart function (46% IVCT) (P < 0.05). Conclusions In a mouse model of GDM, dietary BBR treatment provided protection from obesity and the development of pancreatic islet and cardiac dysfunction.
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Maternal administration of natural compounds could also protect offspring from cardiovascular dysfunction through direct effects on the heart or by mitigating GDM-induced obesity or other cardiometabolic conditions.
“Therefore, maternal administration of natural compounds could also protect offspring from cardiovascular dysfunction through direct effects on the heart or by mitigating GDM-induced obesity or other cardiometabolic conditions.”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [142]
Compared to GDM offspring fed a postnatal high-fat-and-sucrose diet, GDM offspring that received berberine in the high-fat-and-sucrose diet had a lower body weight.
“Compared to GDM offspring fed a postnatal high-fat-and-sucrose diet, the GDM offspring that received berberine in the high-fat-and-sucrose diet had a lower body weight, increased pancreatic islet glucose-stimulated insulin secretion and improved systolic and diastolic heart function [142].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [142]
Compared to GDM offspring fed a postnatal high-fat-and-sucrose diet, GDM offspring that received berberine in the high-fat-and-sucrose diet had improved systolic and diastolic heart function.
“Compared to GDM offspring fed a postnatal high-fat-and-sucrose diet, the GDM offspring that received berberine in the high-fat-and-sucrose diet had a lower body weight, increased pancreatic islet glucose-stimulated insulin secretion and improved systolic and diastolic heart function [142].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [142]
Compared to GDM offspring fed a postnatal high-fat-and-sucrose diet, GDM offspring that received berberine in the high-fat-and-sucrose diet had increased pancreatic islet glucose-stimulated insulin secretion.
“Compared to GDM offspring fed a postnatal high-fat-and-sucrose diet, the GDM offspring that received berberine in the high-fat-and-sucrose diet had a lower body weight, increased pancreatic islet glucose-stimulated insulin secretion and improved systolic and diastolic heart function [142].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [142]
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- Authors
- Cole, L. K., Zhang, M., Chen, L., Sparagna, G. C., Vandel, M., Xiang, B., Dolinsky, V. W., & Hatch, G. M.
- Affiliations
- Children's Hospital Research Institute of Manitoba (CA)
- Jilin University (CN)
- University of Colorado Anschutz (US)
- Corresponding author
- Hatch, Grant M
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 151
- Issue
- 4
- Pages
- 892-901
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W3122503354
- Cited by
- 18
- References
- 45
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 1
- Type
- supplementary materials
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada (144626)
- Canada Foundation for Innovation
- Canada Research Chairs
- Manitoba Medical Services Foundation
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Keywords
- berberine, gestational diabetes mellitus, high-fat diet, offspring metabolic programming, obesity, cardiac dysfunction, glucose-stimulated insulin secretion, pancreatic islets, isovolumic contraction time, metabolic syndrome, dietary supplementation, isoflavones, isoflavone glycosides, isoflavone glucosides
- MeSH terms
- Animals, Berberine, Body Weight, Female, Glucose, Heart Diseases, Insulin, Islets of Langerhans, Male, Mice, Inbred C57BL, Mitochondria, Heart, Obesity, Pregnancy, Prenatal Exposure Delayed Effects, Diabetes, Gestational, Dietary Supplements, Adiposity, Mice, Diet, High-Fat
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