The parallel global increase in obesity and Alzheimer’s disease (AD) underscores an urgent public health challenge, with converging evidence indicating that metabolic dysfunction strongly contributes to neurodegeneration. Obesity is now recognized not only as a systemic metabolic condition but also as a modifiable risk factor for AD, acting through mechanisms such as chronic low-grade inflammation, insulin resistance, and adipose tissue dysfunction. Among the molecular mediators at this interface, adipokines have emerged as pivotal regulators linking metabolic imbalance to cognitive decline. Adipokines are hormone-like proteins secreted by adipose tissue, including adiponectin, leptin, and resistin, that regulate metabolism, inflammation and can influence brain function. Resistin, frequently elevated in obesity, promotes neuroinflammation, disrupts insulin signaling, and accelerates β-amyloid (Aβ) deposition and tau pathology. Conversely, adiponectin enhances insulin sensitivity, suppresses oxidative stress, and supports mitochondrial and endothelial function, thereby exerting neuroprotective actions. The imbalance between resistin and adiponectin may shift the central nervous system toward a pro-inflammatory and metabolically compromised state that predisposes to neurodegeneration. Beyond their mechanistic relevance, adipokines hold translational promise as biomarkers for early risk stratification and therapeutic monitoring. Importantly, natural compounds, including polyphenols, alkaloids, and terpenoids, have shown the capacity to modulate adipokine signaling, restore metabolic homeostasis, and attenuate AD-related pathology in preclinical models. This positions adipokines not only as pathogenic mediators but also as therapeutic targets at the intersection of diabetes, obesity, and dementia. By integrating mechanistic, clinical, and pharmacological evidence, this review emphasizes adipokine signaling as a novel axis for intervention and highlights natural compound-based strategies as emerging therapeutic approaches in obesity-associated AD. Beyond nutraceuticals, antidiabetic agents also modulate adipokines and AD-relevant pathways. GLP-1 receptor agonists, metformin, and thiazolidinediones tend to increase adiponectin and reduce inflammatory tone, while SGLT2 and DPP-4 inhibitors exert systemic anti-inflammatory and hemodynamic benefits with emerging but still limited cognitive evidence. Together, these drug classes offer mechanistically grounded strategies to target the adipokine–inflammation–metabolism axis in obesity-associated AD.

The global prevalence of obesity continues to rise and is a significant risk factor for the onset and progression of cardiovascular diseases. Despite the development of new pharmacological therapies, novel strategies are being explored to mitigate the impact of this disease. Intermittent fasting (IF) is a nutritional intervention that has gained popularity and shows potential as an innovative approach to weight management. This study aims to compile scientific evidence on various aspects of fasting, including its physiological effects, the molecular and thermogenic mechanisms involved, and recommendations regarding nutritional strategies during the refeeding period within the eating window. We conducted a narrative review, analyzing evidence available from PubMed/MEDLINE based on studies related to intermittent fasting, thermogenesis, and their associated outcomes. Our results demonstrate the existence of three commonly used IF protocols: alternate day fasting (ADF), periodic fasting (PF), and time-restricted eating (TRE). In addition to its effects on weight loss, IF has demonstrated notable benefits for cardiovascular health, oxidative stress, and metabolic function. Moreover, the interaction between the central nervous system and brown adipose tissue provides an alternative mechanism for the molecular regulation of thermogenesis. Nutritional patterns adopted during intermittent fasting play a crucial role in optimizing outcomes, with particular emphasis on the intake of proteins, fiber, bioactive compounds, and essential fatty acids during the feeding window. In summary, current evidence indicates that intermittent fasting provides a biologically robust framework for studying energy balance and holds promise for developing targeted nutritional interventions.

Emerging evidence implicates metabolic dysfunction as a key contributor to Alzheimer’s disease (AD) pathogenesis. Fructose, a major component of modern diets, promotes systemic metabolic alterations; however, its direct impact on AD-related brain dysfunction remains poorly defined. Here, we investigated the effects of short-term fructose consumption on systemic metabolism, brain glucose handling, and cognitive performance in APP/PS1 transgenic mice. Six-month-old asymptomatic male mice received 15% fructose in drinking water for eight weeks, while controls received plain water. Fructose-fed APP/PS1 mice developed metabolic alterations consistent with early metabolic syndrome, including increased fasting glucose and dyslipidemia. These changes were accompanied by reduced cerebral glucose utilization, increased Aβ₄₂ accumulation, and impaired cognitive performance. In parallel, fructose intake enhanced neuroinflammatory markers, suggesting a coordinated disruption of metabolic and inflammatory pathways in the brain. Collectively, these findings support the idea that fructose consumption may exacerbate Alzheimer-like alterations linking systemic metabolic dysfunction to impaired brain glucose metabolism and neuroinflammation. This study provides mechanistic evidence supporting a role for dietary fructose as a modifiable risk factor in AD vulnerability.

Background/Objectives: Astrocytes are key regulators of brain energy homeostasis, integrating glucose metabolism with antioxidant support for neuronal function. Dysregulation of these processes contributes to neurodegenerative diseases, including Alzheimer’s disease. Andrographolide, a bioactive diterpenoid from Andrographis paniculata, has been reported to exert neuroprotective effects through the modulation of Wnt/β–catenin signaling and neuronal metabolism; however, its actions on astrocytic metabolic pathways remain insufficiently characterized. Methods: Here, we investigated the effects of andrographolide on metabolic and redox parameters in primary mouse cortical astrocytes. Results: Andrographolide increased glucose uptake and antioxidant capacity without affecting AMPK activation or the activity of core glycolytic enzymes. Instead, it selectively enhanced glucose-6-phosphate dehydrogenase activity, promoting glucose flux through the pentose phosphate pathway in a partially Wnt-dependent manner. This metabolic reprogramming was associated with increased NADPH availability and glutathione levels, together with a reduced ATP/ADP ratio, consistent with a shift toward redox maintenance rather than maximal energy production. Conclusions: Collectively, these findings highlight astrocytic metabolic plasticity as a relevant and underexplored target of andrographolide and support the concept that natural compounds can enhance brain resilience by modulating glial redox metabolism.

Intermittent fasting (IF) has gained increasing attention as a dietary strategy to improve metabolic health and prevent cardiometabolic disorders. Accumulating evidence suggests that modulation of the gut microbiota may represent one of the mechanisms underlying the physiological benefits of IF. This review summarizes the current knowledge on the mechanisms by which IF modulates gut microbial ecology and how these changes influence host metabolic and immune functions. We examine the effects of IF on gut microbiota diversity and composition, highlighting shifts in key microbial taxa associated with metabolic regulation. In addition, we discuss how fasting-induced microbial remodeling affects microbiota-derived metabolites, including short-chain fatty acids and bile acids, which play central roles in energy homeostasis, intestinal barrier integrity, and inflammatory signaling. Increasing evidence indicates that IF interacts with circadian rhythms, influencing both microbial oscillations and host metabolic pathways that coordinate nutrient sensing and energy metabolism. Furthermore, we explore the bidirectional crosstalk between the gut microbiota and the intestinal immune system, emphasizing that fasting-driven microbial changes may modulate inflammatory responses, epithelial barrier function, and immune cell activity. Finally, we discuss nutritional strategies that may enhance the beneficial effects of IF, including the incorporation of prebiotics, dietary fiber, and probiotic supplementation, to promote microbial diversity and functional resilience. Collectively, these findings support a model in which IF acts as a key modulator of the gut microbiota–immune–metabolic axis. Future integrative studies combining gut microbiome, metabolomic, and immunological approaches are needed to better understand these interactions and optimize microbiota-targeted dietary interventions.

Dietary factors may influence cognitive aging and Alzheimer’s disease (AD), but observational associations, mechanistic findings, and intervention effects should not be considered equivalent evidence. This critical narrative review examines how dietary patterns, micronutrient adequacy, and metabolic health may modify AD-related vulnerability. A targeted search of PubMed/MEDLINE, Scopus, and Web of Science through April 2026 prioritized systematic reviews, meta-analyses, randomized trials, and prospective cohorts. Mediterranean, Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND), and healthful plant-based dietary patterns have been associated with better cognitive outcomes and lower dementia risk. However, evidence remains predominantly observational, and randomized trials have not consistently demonstrated prevention of cognitive decline. Strict vegan diets have not shown additional protection beyond high-quality plant-based diets and require careful attention to vitamin B12 and overall nutritional adequacy. Ketogenic diets and medium-chain triglycerides may increase cerebral ketone availability, but their cognitive benefits remain inconsistent, and disease modification has not been established. Although vitamin B12, folate, and vitamin D support neural and metabolic functions, correcting deficiency should not be equated with treating AD. Overall, nutrition should be viewed as a contributor to cardiometabolic and neurological resilience and as part of person-centered dementia care, rather than as a stand-alone disease-modifying therapy. Future studies should integrate accurate dietary assessment, objective adherence measures, metabolic phenotyping, AD biomarkers, and clinically meaningful outcomes.