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

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.

Keywords: fatty-acids; insulin-resistance; menopause; models; obesity; swine.

Figure 1

Individual plasma progesterone concentrations over time of study (left hand) and picture of the ovaries at 120 days (right hand) in sows used as controls (A and a) or treated with two doses of Vacsincel^® for inducing ovarian inactivity (B and b); arrows indicate timing of treatment).

Figure 2

Mean values (± S.E.M.), over time of study, of body mass (A) and depth of total (B) and outer and inner layers (C,D) of subcutaneous backfat depots in sows used as controls (discontinuous line) or treated with two doses of Vacsincel^® for inducing ovarian inactivity (continuous line; arrows indicate timing of treatment). The inset graphs represent the relative increases when compared to the previous assessment (white group CON, black group MEN); units are the same than in the main graph. Asterisks indicate significant differences between groups (* p < 0.05).

Figure 2

Mean values (± S.E.M.), over time of study, of body mass (A) and depth of total (B) and outer and inner layers (C,D) of subcutaneous backfat depots in sows used as controls (discontinuous line) or treated with two doses of Vacsincel^® for inducing ovarian inactivity (continuous line; arrows indicate timing of treatment). The inset graphs represent the relative increases when compared to the previous assessment (white group CON, black group MEN); units are the same than in the main graph. Asterisks indicate significant differences between groups (* p < 0.05).

Figure 3

Mean values (± S.E.M.), over time of study, in mean plasma concentrations (± S.E.M.) for glycemic and lipidic metabolic parameters in sows used as controls (group CON; white bars) or treated with two doses of Vacsincel^® for inducing ovarian inactivity (group MEN; black bars); GLU: glucose (A); FRU: fructosamine (B); CHO: total cholesterol (C); HDL and LDL: high- and low-density lipoproteins cholesterol, respectively (D and E respectively); NEFA: non-esterified fatty acids (F).

Figure 3

Mean values (± S.E.M.), over time of study, in mean plasma concentrations (± S.E.M.) for glycemic and lipidic metabolic parameters in sows used as controls (group CON; white bars) or treated with two doses of Vacsincel^® for inducing ovarian inactivity (group MEN; black bars); GLU: glucose (A); FRU: fructosamine (B); CHO: total cholesterol (C); HDL and LDL: high- and low-density lipoproteins cholesterol, respectively (D and E respectively); NEFA: non-esterified fatty acids (F).

Figure 4

Mean values (± S.E.M.), over time of study, in mean plasma concentrations (± S.E.M.) for metabolic parameters in sows used as controls (group CON; white bars) or treated with two doses of Vacsincel^® for inducing ovarian inactivity (group MEN; black bars); BHB: β-hydroxybutyrate (A); LAC: lactate (B); UREA: urea (C) HAP: haptoglobin (D). Asterisks indicate significant differences between groups (* p < 0.05; ** p < 0.01; *** p < 0.005).