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Puberty as a DOHaD programming window: High-fat diet induces long-term hepatic dysfunction in male rats

journal contribution
posted on 2023-12-06, 05:03 authored by BG Dos Santos, RA Miranda, LPJ Saavedra, FA Francisco, MVG Ribeiro, AR Oliveira Ferreira, MD Ferreira-Junior, KVN Cavalcante, CH Xavier, EG De Moura, PC Lisboa, APCD Mota, GR Pedrino, James ArmitageJames Armitage, PCDF Mathias, K Palma-Rigo, RM Gomes
The aim of this study was to evaluate whether high-fat (HF) diet intake during puberty can program obesity as well as generate glucose imbalance and hepatic metabolic dysfunctions in adult life. Male Wistar rats were randomly assigned into two groups: rats fed standard chow (NF) and rats fed a HF from postnatal 30-day-old (PND30) until PND60. Then, both groups were fed a standard chow from PND60 until PND120. Euthanasia and samples collections occurred at PND120. HF animals were overweight (+11%) and had increased adiposity, hyperphagia (+12%), hyperglycaemia (+13%), hyperinsulinemia (+69%), and hypertriglyceridemia (+34%). Plasma glucose levels during intravenous glucose tolerance test (ivGTT) and intraperitoneal insulin tolerance test (ipITT) were also higher in the HF group, whereas Kitt was significantly lower (-34%), suggesting reduced insulin sensitivity. In the same sense, HF animals present pancreatic islets hypertrophy and high β-cell mass. HF animals also had a significant increase in blood glucose levels during pyruvate tolerance test, indicating increased gluconeogenesis. Hepatic morphology analyses showed an increase in lipid inclusion in the HF group. Moreover, PEPCK and FAS protein expression were higher in the livers of the HF animals (+79% and + 37%, respectively). In conclusion, HF during puberty causes obese phenotype leading to glucose dyshomeostasis and nonalcoholic fatty liver disease, which can be related to the overexpression of proteins PEPCK and FAS.

History

Journal

Journal of Developmental Origins of Health and Disease

Location

England

ISSN

2040-1744

eISSN

2040-1752

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Publisher

CAMBRIDGE UNIV PRESS