Nutrients

Background/Objectives: Skeletal muscle–derived myokines have emerged as pivotal mediators of the muscle–brain axis, linking peripheral metabolic regulation with central nervous system function. These molecules may influence skeletal muscle maintenance, neuroplasticity, neuroinflammation, and cognitive performance, and their dysregulation is increasingly associated with metabolic and cognitive impairment. In obesity (OB) and type 2 diabetes mellitus (T2DM), dysregulated myokine profiles characterized by reduced levels of irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B (CTSB) have been reported and may contribute to the development of both sarcopenia and cognitive impairment. This review aims to summarize current evidence on myokine alterations in OB and T2DM and to evaluate how exercise- and nutrition-based interventions may modulate the muscle–brain axis to support metabolic and cognitive health. Methods: This narrative review synthesizes experimental, clinical, and translational studies examining (1) alterations in circulating myokines in OB and T2DM, (2) associations between myokines, skeletal muscle function, and neurocognitive outcomes, and (3) the modulatory effects of exercise and specific nutrients on myokine-mediated muscle–brain communication. Results: Available evidence indicates that OB and T2DM are frequently accompanied by reduced circulating levels of beneficial myokines such as irisin, BDNF, and CTSB, which may impair skeletal muscle integrity and contribute to cognitive decline. Restoring favorable myokine signaling through physical activity appears to enhance skeletal muscle maintenance, neuroplasticity, and metabolic homeostasis. Emerging data further suggest that selected nutrients can mimic or potentiate some exercise-induced myokine responses, thereby supporting both muscle and brain function. Collectively, these findings imply that combined exercise and nutrition strategies may exert synergistic or additive effects by reinforcing inter-organ communication along the muscle–brain axis. Conclusions: This review outlines current evidence on myokine alterations observed in OB and T2DM and discusses how exercise- and nutrition-based approaches may modulate the muscle–brain axis to mitigate metabolic dysfunction and preserve cognitive health. Targeting beneficial myokine pathways through tailored lifestyle interventions represents a promising avenue to support both skeletal muscle and neurocognitive function in individuals with metabolic disease.

Background: Obesity is a risk factor for several non-communicable diseases and premature death. The Western-type diet, rich in calories and diverse in tastes, smells, and textures, promotes the onset and progression of obesity. We compared the effects of two Western-style palatable obesogenic diets—the cafeteria (CAF) diet, which allows for self-selection of calorie-dense food items consumed by humans, and the fast-food diet (FFD)—composed of a fixed combination of cheeseburgers and fries—on the manifestation of obesity-related complications. Methods: 3-month-old female rats consumed either the control (CTRL), FFD, or CAF diet for 12 months. Body weight was monitored weekly. At the end of the experiment, rats underwent metabolic and behavioral testing. Cardiometabolic markers and those characterizing glycoxidative and carbonyl stress, inflammatory status, and tryptophan metabolism were determined. Results: The CAF rats gain most weight (CTRL: +111 ± 40 g; FFD: +211 ± 77 g; CAF: 316 ± 87 g). CAF feeding produced a classical metabolic syndrome–like profile with severe obesity, insulin resistance, dyslipidemia, and liver steatosis, whereas the FFD model led to moderate obesity with preserved insulin sensitivity but elevated blood pressure and hepatic cholesterol accumulation. Thus, the CAF group developed a severe metabolic syndrome-like pathology assessed as continuous metabolic syndrome z-core (CTRL: −2.3 ± 1.0; FFD: −0.4 ± 1.9; CAF: 3.0 ± 2.4). Despite these differences, both diets promoted neuroinflammation and social deficits, likely mediated through gut microbiota–derived metabolites such as 5-HIAA and indoxyl sulfate. Conclusions: In female rats, self-selected CAF diet drives more severe and distinct pattern of metabolic syndrome-like pathology than a fixed FFD.

Background/Objectives: As high salt intake may increase obstructive sleep apnea (OSA) risk through fluid retention and upper airway narrowing during sleep, we aimed to determine whether dietary salt intake modified the association between menopausal transition and the risk of OSA. Methods: Between 2014 and 2018, we conducted a longitudinal study of 2572 women aged 42–52 years at the Kangbuk Samsung Hospital Total Healthcare Center. The participants were followed up until the end of 2024. OSA risk was evaluated using the STOP-Bang questionnaire, with a body mass index threshold adjusted to ≥30 kg/m² in accordance with a Korean validation study. Dietary salt intake was categorized into tertiles, with tertile 3 representing the highest salt intake. Generalized estimating equations with time-dependent covariates were used to account for repeated measurements over time. Results: OSA risk increased during menopausal transition. Compared with the pre-menopausal stage, both late transition (β = 0.41, 95% confidence interval [CI] 0.05–0.78) and post-menopause (β = 0.61, 95% CI 0.20–1.02) were significantly associated with an increased risk of OSA, independent of potential confounders. A high salt intake (tertile 3) was also significantly associated with OSA. A significant interaction was observed between menopausal transition and salt intake (p = 0.040), with a stronger association between menopausal transition and OSA during the early transition stage in women with higher salt intake. Conclusions: Menopausal transition and high dietary salt intake appear to act synergistically to increase the risk of OSA in middle-aged women. Our results suggest that implementing targeted screening and reducing dietary salt intake may mitigate the risk of OSA during menopausal transition.