Menopause-induced changes may include increased incidence of both depression/anxiety and obesity. We hypothesized that behavioral changes that may develop after ovarian failure could be related to neurochemical and metabolic aspects affected by this condition and that high-fat intake may influence these associations. The present study investigated in rats the effects of ovariectomy, either alone or combined with high-fat diets enriched with either lard or fish-oil, on metabolic, behavioral and monoaminergic statuses, and on gene expression of neuropeptides and receptors involved in energy balance and mood regulation. Female rats had their ovaries removed and received either standard chow (OvxC) or high-fat diets enriched with either lard (OvxL) or fish-oil (OvxF) for 8 weeks. The Sham group received only chow diet. Ovariectomy increased feed efficiency and body weight gain and impaired glucose homeostasis and serotonin-induced hypophagia, effects either maintained or even accentuated by the lard diet but counteracted by the fish diet. The OvxL group developed obesity and hyperleptinemia. Regarding components of hypothalamic serotonergic system, both ovariectomy alone or combined with the fish diet increased 5-HT2C expression while the lard diet reduced 5-HT1B mRNA. Ovariectomy increased the anxiety index, as derived from the elevated plus maze test, while both high-fat groups showed normalization of this index. In the forced swimming test, ovariectomy allied to high-lard diet, but not to fish-oil diet, reduced the latency to immobility, indicating vulnerability to a depressive-like state. Linear regression analysis showed hippocampal AgRP to be negatively associated with the anxiety index and hypothalamic AgRP to be positively associated with the latency to immobility. These AgRp gene expression associations are indicative of a beneficial involvement of this neuropeptide on both depression and anxiety measures. The present findings demonstrate metabolic, neurochemical and behavioral alterations after ovaries removal and highlight a positive effect of high-fat feeding on the anxiety-like behavior shown by ovariectomized animals. Since the polyunsaturated ômega-3 intake (fish diet), unlike the saturated fat intake (lard diet), failed to induce deleterious metabolic or neurochemical consequences, further studies are needed focusing on the potential of this dietary component as an adjuvant anxiolytic agent after menopause.

Hyperleptinemia has emerged as a marker of proinflammatory status, while the adiponectin/leptin ratio has been used to identify anti-inflammatory state. In this context, the aims of the present study were to investigate the role of leptinemia, adjusted by tertiles, on inflammatory state in obese adults according to obesity degree. This is a cross-sectional study comprised of 43 obese adults. The anthropometric variables and body composition were analyzed, as well as markers of inflammation such as leptin, adiponectin, and plasminogen activator inhibitor. Subjects were grouped using adjusted tertiles of the leptin levels. The major finding was the negative correlation between leptin concentration with adiponectin/leptin ratio (r=-0.622, p=0.000) and the positive correlation with leptin/adiponectin ratio (r=0.622, p=0.000). Indeed, both ratios were decreased and increased, respectively, according to the obesity degree. Furthermore, in the stepwise multiple linear regression analysis, the high degree of obesity was an independent predictor of leptinemia when adjusted for age and BMI (β=0.588, p=0.000 and β=0.778, p=0.005). Finally, the strong negatively correlation between the leptinemia with adiponectin/leptin ratio and the positive correlation with leptin/adiponectin ratio reinforce the role of this adipokine as a biomarker of inflammation in obese adults, according to obesity degree. Our findings can elucidate that hyperleptinemic status was a major factor in the proinflammatory status related to higher obesity degree. All together, these data reinforce the role of leptinemia state as a mediator of inflammation in obese adults.

While several pieces of evidence link obesity and mood disorders in menopause, the mechanisms involved are not yet fully understood. We have previously demonstrated that Ginkgo biloba extract (GbE) both attenuated diet-induced obesity of male rats and restored serotonin-induced hypophagia in ovariectomized female rats. The present study aimed at exploring whether GbE treatment ameliorates ovariectomy-related obesity and anxious/depressive-like behaviours. Wistar female rats were either ovariectomized (OVX) or sham-operated (Sham). After 2 months, either 500 mg/kg of GbE or vehicle were administered daily by gavage for 14 days. Anxious/depressive-like behaviours were assessed by the Elevated Plus Maze and the Forced Swim Tests, respectively. Ovariectomy caused high visceral adiposity, hyperleptinemia, and hypercholesterolemia, and increased the anxiety index (p = 0.048 vs. Sham + GbE) while it decreased the latency to immobility (p = 0.004 vs. Sham). GbE treatment in OVX rats improved body composition, adiponectin levels and blood lipid profile. It also reduced the anxiety index (p = 0.004) and increased the latency to immobility (p = 0.003) of OVX rats. Linear regression analysis demonstrated that leptin (p = 0.047) and total cholesterol levels (p = 0.022) were associated with anxious-like behaviours while body adiposity (p = 0.00005) was strongly associated with depressive-like behaviours. The results showed that GbE therapy was effective in attenuating the deleterious effects of ovariectomy on body composition, lipid profile, and anxious/depressive-like behaviours. Further studies are warranted to better understand the therapeutic potential of GbE in menopause.

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