The etiology of metabolic disorders, such as obesity, has been predominantly associated with the gut microbiota, which is acknowledged as an endocrine organ that plays a crucial role in modulating energy homeostasis and host immune responses. The presence of dysbiosis has the potential to impact the functioning of the intestinal barrier and the gut-associated lymphoid tissues by allowing the transit of bacterial structural components, such as lipopolysaccharides. This, in turn, may trigger inflammatory pathways and potentially lead to the onset of insulin resistance. Moreover, intestinal dysbiosis has the potential to modify the production of gastrointestinal peptides that are linked to the feeling of fullness, hence potentially leading to an increase in food consumption. In this literature review, we discuss current developments, such as the impact of the microbiota on lipid metabolism as well as the processes by which its changes led to the development of metabolic disorders. Several methods have been developed that could be used to modify the gut microbiota and undo metabolic abnormalities. Methods: After researching different databases, we examined the PubMed collection of articles and conducted a literature review. Results: After applying our exclusion and inclusion criteria, the initial search yielded 1345 articles. We further used various filters to narrow down our titles analysis and, to be specific to our study, selected the final ten studies, the results of which are included in the Results section. Conclusions: Through gut barrier integrity, insulin resistance, and other influencing factors, the gut microbiota impacts the host’s metabolism and obesity. Although the area of the gut microbiota and its relationship to obesity is still in its initial stages of research, it offers great promise for developing new therapeutic targets that may help prevent and cure obesity by restoring the gut microbiota to a healthy condition.

The global rise in type 2 diabetes mellitus (T2DM) calls for an urgent focus on lifestyle interventions, particularly physical activity, as a critical factor in its management and prevention. This systematic review evaluates the impact of physical activity and sedentary behavior on glycemic control in individuals with T2DM. Studies included in this review were selected based on specific criteria: randomized controlled trials involving adults aged 18 and older, published in English between January 2018 and May 2024, with full-text availability and quantifiable outcome results. Exclusion criteria included non-peer-reviewed research, small sample sizes, and studies limited to abstracts, posters, or editorials. The analysis of the selected studies revealed that regular physical activity, including aerobic exercises and resistance training, significantly improves glycemic control as measured by fasting blood glucose (FBG) and glycated hemoglobin (HbA1C) levels. Reductions in sedentary behavior were also associated with better metabolic outcomes, highlighting the importance of integrating physical activity into daily routines for individuals with T2DM. These findings feature the need for continued research to refine and optimize lifestyle interventions to mitigate the global burden of T2DM.

Oxidative stress is an important component of cancer biology and is characterized by an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems. Excess ROS can cause molecular damage and genomic instability; at the same time, ROS signaling remains necessary for normal cellular function. Redox homeostasis is of particular importance in this balance. The aim of this structured narrative review was to summarize and critically discuss current evidence on how dietary antioxidants influence redox-sensitive pathways involved in cancer prevention, with particular attention to metabolic inflammation, mitochondrial quality control, and gut microbiota-related mechanisms. We performed a structured literature search of Scopus, Web of Science, and PubMed, focusing on articles published between 2021 and 2026. The evidence covered major redox-sensitive pathways, including Nrf2-Keap1-ARE signaling, AMPK-mTOR regulation, NF-κB-mediated inflammation, mitochondrial quality control (autophagy and mitophagy), and inflammasome activation. These pathways, which are involved in tumor initiation and progression, link oxidative stress to metabolic and inflammatory processes. Current evidence suggests that dietary antioxidants act primarily by supporting endogenous defense systems. This may help explain the “antioxidant paradox”, in which antioxidant-rich dietary patterns are associated with a lower risk of cancer. In some studies, high-dose supplementation with isolated antioxidants has produced inconsistent or sometimes adverse results. These effects depend on dose, chemical form, metabolic context, and baseline redox state. The gut microbiota is also an important mediator of antioxidant bioactivity; by converting dietary polyphenols into bioactive metabolites, it can influence systemic redox balance and metabolic signaling. This microbiota-dependent modulation may partially explain inter-individual variability in responses to dietary interventions. In conclusion, dietary antioxidants should be considered as modulators of redox-sensitive signaling networks, not merely as simple radical scavengers. Personalized modulation of redox homeostasis is a future strategy for cancer prevention, with a greater emphasis on whole-diet and biomarker-guided approaches.

Oxidative stress is an important component of cancer biology with an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems. Excess ROS can cause molecular damage and genomic instability. At the same time, ROS signaling remains necessary for normal cellular function. Redox homeostasis is of particular importance in this balance. The role of dietary antioxidants in cancer prevention is complex, depending on the biological context. This narrative review used preclinical and clinical studies to synthetize the current literature. We performed an extensive literature search of Scopus, Web of Science, and PubMed. We focused on articles published between 2021 and 2026. Dietary antioxidants influence redox biology in cancer. It focuses on major redox-sensitive pathways, including Nrf2-Keap1-ARE signaling, AMPK-mTOR regulation, NF-κB-mediated inflammation, mitochondrial quality control (autophagy and mitophagy), and inflammasome activation. These pathways involved in tumor initiation and progression link oxidative stress to metabolic and inflammatory processes. Current evidence suggests that dietary antioxidants act primarly by supporting endogenous defense systems. This may help explain the “antioxidant paradox,” in which antioxidant-rich dietary patterns are associated with a lower risk of cancer. In some studies, high-dose supplementation with isolated antioxidants has produced inconsistent or sometimes adverse results. These effects depend on dose, chemical form, metabolic context, and initial redox state. The gut microbiota is also an important mediator of antioxidant bioactivity. The gut microbiota modulates systemic redox balance by converting dietary polyphenols into bioactive metabolites, not acting only as simple scavengers. This contributes to inter-individual variability. Dietary antioxidants act as modulators of redox signaling. Personalized redox modulation may guide future cancer prevention strategies, emphasizing whole-diet approaches and biomarkers.

Cellular stress is not inherently detrimental; its biological consequences depend on intensity, duration, context, and the capacity for recovery. This narrative review proposes the Burn-ON/Burn-OUT paradigm as a hypothesis-generating framework describing the transition from adaptive cellular activation to progressive loss of cellular resilience. A structured literature search was conducted for English-language articles published between 2021 and 2026 in PubMed, Web of Science, and Scopus, focusing on cellular stress adaptation, mitochondrial dysfunction, integrated stress response, autophagy and mitophagy, redox signaling, inflammasome activation, metabolic flexibility, senescence, and nutritional modulation. In the proposed model, Burn-ON represents a state of increased cellular demand in which mitochondrial adaptation, stress-response signaling, autophagic quality control, redox homeostasis, and metabolic flexibility remain sufficiently preserved to sustain function and allow recovery. With persistent or repetitive stress, these adaptive mechanisms may progressively lose reversibility, defining a potential tipping point toward Burn-OUT. Burn-OUT is characterized conceptually by impaired mitochondrial quality control, reduced energetic reserve, defective autophagic flux, persistent inflammatory signaling, redox imbalance, metabolic inflexibility, and loss of functional recovery, with senescence or regulated cell death representing possible downstream outcomes. Nutrition and lifestyle may modulate this continuum by influencing nutrient sensing, substrate load, mitochondrial metabolism, autophagy, and inflammatory pathways. The Burn-ON/Burn-OUT model frames cellular stress as a double-edged biological process, in which adaptation and dysfunction represent different positions along a dynamic continuum. Longitudinal studies are needed to determine whether recovery kinetics and multidimensional biomarker profiles can distinguish these proposed states.

Body mass index (BMI) is widely used in clinical practice, but it does not directly reflect fat distribution, ectopic adiposity, or adipose tissue function. Individuals with a normal or near-normal BMI may still have excess visceral fat. The Thin Outside, Fat Inside (TOFI) phenotype describes this mismatch between external body size and internal adiposity. This structured narrative review examined TOFI and related normal-weight phenotypes, focusing on visceral and ectopic fat, adipose tissue dysfunction, molecular mechanisms, imaging, and organ-specific risk. A literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science for English-language studies published mainly between 2021 and 2026. Earlier seminal and directly relevant studies were also included. Evidence from related human phenotypes and experimental models suggests that impaired adipose tissue expandability, visceral and ectopic fat accumulation, inflammation, mitochondrial stress, and lipotoxicity may help explain metabolic dysfunction despite a normal BMI. These mechanisms remain incompletely characterized in populations explicitly defined as TOFI. Preclinical models and imaging methods may help characterize TOFI-like features. Diagnostic criteria are still heterogeneous, and TOFI-specific longitudinal and intervention data remain limited. TOFI may serve as a useful translational framework for identifying hidden adiposity and metabolic risk in individuals with a normal BMI.