Nutritional strategies based on the combined supplementation of bioactive compounds to ameliorate obesity and metabolic alterations occurring at key stages of female reproductive aging

Identifier:  TDX:4505

Handle: https://hdl.handle.net/20.500.11797/TDX4505

Authors:  Baudin Luque, Julio Carlos

Abstract:
Menopausal transition, known as perimenopause, and later, the postmenopausal state are natural biological phases in a woman’s life associated with reproductive aging. These processes are characterized by senescence in the ovarian function accompanied by a decline in oestrogen production, which already occurs in perimenopause with the appearance of irregular menstrual cycles and is exacerbated during the postmenopausal state. This reproductive aging process is often accompanied by various vasomotor symptoms, such as sleep disturbances, night sweats, and hot flashes, and can be associated with an increased risk of osteoporosis and with the appearance of obesity and other cardiovascular risk factors. In this PhD thesis, we hypothesized that two multi-ingredients acting against complementary targets, one containing the natural bioactive compounds curcumin, hesperidin, and phytosterols, and the other composed of the amino acid-related compounds histidine, serine, cysteine, and carnosine can exert beneficial effects against obesity and related cardiometabolic disturbances associated with menopause. We firstly characterized the menopausal transition using ovarian-intact middle-aged rats and analyzed circulating signatures across perimenopause, identifying potential lipidomic-based biomarkers in serum during the menopausal transition. Secondly, we used ovariectomized rats, a postmenopausal model with oestrogen deficiency, and we reported, using a transcriptomics approach, that peripheral blood mononuclear cells reflected the molecular changes associated with oestrogen deficiency in the postmenopausal stage concerning alterations in immune function, stress response, bone metabolism, cholesterol metabolism, and glucose homeostasis. Finally, we revealed that the oral supplementation with the two above commented multi-ingredients ameliorated obesity and related metabolic alterations in ovariectomized rats, being these effects of a similar magnitude to those produced by the administration of oestradiol, a pharmacological treatment that simulates hormone replacement therapy that is sometimes prescribed to women during the post-menopausal state. Our findings can pave the way for using these multi-ingredient-based formulations as alternative therapies to manage menopausal-related disturbances.