Short-Term Effects of Early Menopause on Adiposity, Fatty Acids Profile and Insulin Sensitivity of a Swine Model of Female Obesity.

Ana Heras-Molina,Consolacion Garcia-Contreras,Susana Astiz,Beatriz Isabel,José Luis Pesantez-Pacheco,Antonio Gonzalez-Bulnes,Marta Vazquez-Gomez

doi:10.3390/biology9090284

Abstract

Menopause strongly increases incidence and consequences of obesity and non-communicable diseases in women, with recent research suggesting a very early onset of changes in lipid accumulation, dyslipidemia, and insulin resistance. However, there is a lack of adequate preclinical models for its study. The present trial evaluated the usefulness of an alternative method to surgical ovariectomy, the administration of two doses of a GnRH analogue-protein conjugate (Vacsincel®), for inducing ovarian inactivity in sows used as preclinical models of obesity and menopause. All the sows treated with the compound developed ovarian stoppage after the second dose and, when exposed to obesogenic diets during the following three months, showed changes in the patterns of fat deposition, in the fatty acids profiles at the different tissues and in the plasma concentrations of fructosamine, urea, β-hydroxibutirate, and haptoglobin when compared to obese fed with the same diet but maintaining ovarian activity. Altogether, these results indicate that menopause early augments the deleterious effects induced by overfeeding and obesity on metabolic traits, paving the way for future research on physiopathology of these conditions and possible therapeutic targets using the swine model.

Highlights

Obesity is currently declared a global pandemic according to WHO because its worldwide incidence has nearly tripled since 1975 and currently at least 4 million people are dying each year as a direct result of the condition
The results of the present study support previous data on the adequacy and reliability of the Iberian pig fed with a high-fat diet as a translational model of obesity
The induction of ovarian failure with the use of this compound in sows treated with an obesogenic diet

Summary

Introduction

Obesity is currently declared a global pandemic according to WHO (https://www.who.int/healthtopics/obesity#tab=tab_1 and http://www.who.int/mediacentre/factsheets/fs311/en/index.html) because its worldwide incidence has nearly tripled since 1975 and currently at least 4 million people are dying each year as a direct result of the condition. Menopause is a critical point for incidence and consequences of obesity and NCDs and, CVD and T2D. In this way, occurrence and severity of CVD and T2D are lower in premenopausal females than in age-matched males, but dramatically increase after menopause [1,2,3]. Estrogen-based replacement therapies in postmenopausal women reduce the incidence of T2D [9,10], but their role in preventing CVD, and their own security, remains highly controversial [5]. Current data highlights the importance of factors related to the treatment (protocol, route, type of steroids) and, mainly, to the age of the woman and the time of initiation of replacement therapy after menopause [11]. Epidemiological studies indicate that beneficial effects are more frequently found with short-term therapies starting at the early post-menopause [12,13,14], which suggest a very early onset of changes in the metabolism of glucose, lipids and fatty acids

Results

Discussion

Conclusion