Novel Lean Type 2 Diabetic Rat Model Using Gestational Low-protein Programming

Overview

Journal Am J Obstet Gynecol

Publisher Elsevier

Specialty Gynecology & Obstetrics

Date 2016 Feb 14

PMID 26874300

Citations 14

Authors

Chellakkan S Blesson

Amy K Schutt

Meena P Balakrishnan

Robia G Pautler

Steen E Pedersen

Poonam Sarkar

Daniel Gonzales

Gang Zhu

Juan C Marini

Shaji K Chacko

Uma Yallampalli

Chandra Yallampalli

Affiliations

Soon will be listed here.

Abstract

Background: Type 2 diabetes (T2D) in lean individuals is not well studied and up to 26% of diabetes occurs in these individuals. Although the cause is not well understood, it has been primarily attributed to nutritional issues during early development.

Objective: Our objective was to develop a lean T2D model using gestational low-protein (LP) programming.

Study Design: Pregnant rats were fed control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery. Standard diet was given to dams after delivery and to pups after weaning. Glucose tolerance test was done at 2, 4, and 6 months of age. Magnetic resonance imaging of body fat for females was done at 4 months. Rats were sacrificed at 4 and 8 months of age and their perigonadal, perirenal, inguinal, and brown fat were weighed and expressed relative to their body weight. Euglycemic-hyperinsulinemic clamp was done around 6 months of age.

Results: Male and female offspring exposed to a LP diet during gestation developed glucose intolerance and insulin resistance (IR). Further, glucose intolerance progressed with increasing age and occurred earlier and was more severe in females when compared to males. Euglycemic-hyperinsulinemic clamp showed whole body IR in both sexes, with females demonstrating increased IR compared to males. LP females showed a 4.5-fold increase in IR while males showed a 2.5-fold increase when compared to their respective controls. Data from magnetic resonance imaging on female offspring showed no difference in the subcutaneous, inguinal, and visceral fat content. We were able to validate this observation by sacrificing the rats at 4 and 8 months and measuring total body fat content. This showed no differences in body fat content between control and LP offspring in either males or females. Additionally, diabetic rats had a similar body mass index to that of the controls.

Conclusion: LP gestational programming produces a progressively worsening T2D model in rats with a lean phenotype without obesity.

Citing Articles

Maternal Low-Protein Diet Leads to Mitochondrial Dysfunction and Impaired Energy Metabolism in the Skeletal Muscle of Male Rats.

Vidyadharan V, Betancourt A, Smith C, Blesson C, Yallampalli C Int J Mol Sci. 2024; 25(23).

PMID: 39684571 PMC: 11641076. DOI: 10.3390/ijms252312860.

Global burden of type 2 diabetes attributable to non-high body mass index from 1990 to 2019.

Wu J, Feng Z, Duan J, Li Y, Deng P, Wang J BMC Public Health. 2023; 23(1):1338.

PMID: 37438808 PMC: 10337097. DOI: 10.1186/s12889-023-15585-z.

Low Protein Programming Causes Increased Mitochondrial Fusion and Decreased Oxygen Consumption in the Hepatocytes of Female Rats.

Vidyadharan V, Blesson C, Tanchico D, Betancourt A, Smith C, Yallampalli C Nutrients. 2023; 15(7).

PMID: 37049409 PMC: 10097083. DOI: 10.3390/nu15071568.

Developmental Programming-Aging Interactions Have Sex-Specific and Developmental Stage of Exposure Outcomes on Life Course Circulating Corticosterone and Dehydroepiandrosterone (DHEA) Concentrations in Rats Exposed to Maternal Protein-Restricted....

Zambrano E, Reyes-Castro L, Rodriguez-Gonzalez G, Chavira R, Lomas-Soria C, Gerow K Nutrients. 2023; 15(5).

PMID: 36904238 PMC: 10005360. DOI: 10.3390/nu15051239.

Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes.

Salvatore T, Galiero R, Caturano A, Rinaldi L, Criscuolo L, di Martino A Int J Mol Sci. 2023; 24(1).

PMID: 36614099 PMC: 9820420. DOI: 10.3390/ijms24010658.

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