POSTMENOPAUSAL women experience significant physiological changes, primarily driven by hormonal shifts, particularly the decline in oestrogen. These changes lead to increased visceral fat accumulation and decreased muscle mass, contributing to systemic inflammation, insulin resistance, and a heightened risk of metabolic syndrome. Addressing these metabolic disturbances is crucial for improving health outcomes, and targeted interventions combining nutrition and exercise are gaining recognition.
Intermittent fasting (IF) has emerged as a promising approach to improving metabolic health and body composition. IF alternates between periods of eating and fasting, with popular methods including the 16:8 protocol and alternate-day fasting. Research indicates that IF enhances metabolic flexibility, allowing the body to switch between glucose and fat as primary fuel sources. This process promotes fat oxidation, improves insulin sensitivity, and reduces inflammation. Cellular responses to fasting, including the activation of AMP-activated protein kinase (AMPK) and autophagy, further support glucose regulation, mitochondrial function, and oxidative stress resistance.
Beyond metabolic benefits, IF influences the neuroendocrine system, particularly the orexinergic system. Orexin-A, a neuropeptide produced in the lateral hypothalamus, plays a pivotal role in regulating energy balance, arousal, and feeding behaviour. During fasting, orexin neurons activate neuropeptide Y (NPY) and agouti-related peptide (AgRP), increasing appetite to restore energy balance while simultaneously stimulating thermogenesis and lipolysis. AMPK, a master regulator of cellular energy, also activates orexin neurons during fasting, enhancing lipid metabolism and mitochondrial biogenesis.
Combining IF with high-intensity interval training (HIIT) may amplify these metabolic and neuroendocrine responses. HIIT, characterised by short bursts of intense exercise followed by recovery periods, is known to improve insulin sensitivity, fat oxidation, and cardiorespiratory fitness. Research suggests that HIIT activates orexinergic pathways by inducing metabolic stress, increasing AMPK activation, and stimulating lipid metabolism and muscle glucose uptake.
The synergy between IF and HIIT engages overlapping metabolic and neuroendocrine pathways. IF promotes metabolic switching, while HIIT triggers acute stress responses via the hypothalamic-pituitary-adrenal axis, stimulating cortisol release and orexin activity to support energy mobilisation. This dual activation may enhance orexin-A levels more effectively than either intervention alone, leading to improved energy homeostasis and motivation for physical activity.
While these findings are promising, further research is needed to explore the long-term effects of IF and HIIT on the orexinergic system, particularly in postmenopausal women. Understanding these interactions could inform personalised strategies to combat metabolic dysfunction, reduce visceral fat, and enhance physical performance, ultimately improving quality of life in this population.
Reference
Valenzano AA et al. Influence of intermittent fasting on body composition, physical performance, and the orexinergic system in postmenopausal women: a pilot study. Nutrients. 2025;17(7):1121.
