Search Results (4,345)

Diabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM), characterized by cardiac dysfunction, inflammation, and fibrosis. In this study, a T2DM mouse model was established by administering a high-fat diet (60% fat) in combination with streptozotocin injection in male C57BL/6J mice. The mice subsequently underwent an eight-week exercise intervention consisting of swimming training, resistance training, or high-intensity interval training (HIIT). The results showed that all three forms of exercise improved cardiac function and attenuated myocardial hypertrophy in DCM mice. Exercise training further downregulated the expression of pro-inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, nuclear factor κB, and monocyte chemoattractant protein-1, and mitigated myocardial fibrosis by suppressing fibronectin, α-SMA, collagen type I alpha 1 chain, collagen type III alpha 1 chain, and the TGF-β1/Smad signaling pathway. Moreover, exercise inhibited the expression of PANoptosis-related genes and proteins in cardiomyocytes of DCM mice. Notably, HIIT produced the most pronounced improvements across these pathological markers. In addition, all three exercise modalities effectively suppressed the aberrant activation of the cGAS–STING signaling pathway in the myocardium. In conclusion, exercise training exerts beneficial effects against DCM by improving cardiac function and reducing inflammation, PANoptosis, and fibrosis, and HIIT emerged as the most effective strategy. Full article

Background/objectives: Individuals with type 1 diabetes (T1DM) face an elevated risk of cardiovascular disease (CVD), yet the factors driving atherosclerosis remain unclear. This study aimed to assess factors associated with preclinical atherosclerosis development or progression in T1DM. Methods: We conducted a prospective study in T1DM individuals without established CVD, aged ≥40 years, with diabetic kidney disease and/or ≥10 years of T1DM plus another cardiovascular risk factor (CVRF). Baseline evaluation followed a standardized CV risk assessment protocol, including carotid ultrasound and cardiovascular risk estimation using the Steno Type 1 Risk Engine (ST1RE). Ultrasound was repeated after 3–5 years; progression was defined as an increase in plaque number. CVRF control was considered optimal when LDL-cholesterol was within target based on atherosclerotic burden, blood pressure <130/80 mmHg, HbA1c <7%, and non-smoking status. Logistic regression models identified predictors of progression. Results: We included 151 participants (55.6% women; mean age 49.8 ± 8.9 years; T1DM duration 27.3 ± 9.1 years); 42.4% had plaques at baseline. Over a follow-up of 5.22 ± 1.29 years, despite improved CVRF control (p < 0.05), 40.4% experienced progression. Older age (OR 1.38 [1.1–1.8]) and active smoking (OR 3.29 [1.4–7.5]) were significant predictors of progression. Baseline cardiovascular risk measured by the ST1RE independently predicted progression (OR 1.09 [1.03–1.15]) after adjusting for other CVRFs. Persistent smoking (OR 2.52 [1.06–5.99]) and baseline ST1RE (OR 1.06 [1.02–1.11]) remained significant after accounting for baseline and follow-up CVRFs. Conclusions: Despite improved CVRF control, atherosclerosis progression is common in T1D. ST1RE may help identify individuals at highest risk for targeted preventive strategies. Full article

This study employs molecular orbital (MO) analysis, density of states (DOS) analysis, and advanced techniques such as charge density difference (CDD), transition density matrix (TDM), transition electric dipole moment density (TEDM), and transition magnetic dipole moment density (TMDM) to systematically investigate the electronic structure characteristics of Fc-[8]CPP and Fc-[11]CPP. Using density functional theory (DFT) and time-dependent DFT (TD-DFT), the π-electron delocalization properties and optical behaviors of these molecules were analyzed. Furthermore, their responses to external electromagnetic fields were explored through electronic circular dichroism (ECD) and Raman spectroscopy, comparing chiral optical responses and electron–vibration coupling effects to elucidate their photophysical properties. The results reveal that the HOMO-LUMO energy gaps of Fc-[8]CPP and Fc-[11]CPP are 5.81 eV and 5.95 eV, respectively, with a slight increase as ring size grows; Fc-[8]CPP exhibits a stronger chiral response, while Fc-[11]CPP shows reduced chirality due to enhanced symmetry. Finally, TD-DFT calculations demonstrate that their optical absorption is dominated by localized excitations with partial charge transfer contributions. These findings provide a theoretical foundation for designing conjugated macrocyclic materials with superior optoelectronic performance. Full article

Type 2 diabetes mellitus (T2DM) is frequently complicated by atherosclerosis (AS), with substantial overlap in their underlying pathophysiological mechanisms, posing serious threats to patient health. Tirzepatide, a novel dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated remarkable efficacy in glycemic control, weight reduction, and cardiometabolic improvement, making it a promising candidate for managing T2DM comorbid with AS. However, substantial interindividual variability in treatment response suggests a role for genetic determinants. This review systematically summarises current evidence on pharmacogenomic variants influencing the efficacy and toxicity of tirzepatide, explores the interplay between drug response genes and genetic susceptibilities to T2DM and AS, and highlights the potential of pharmacogenomics in guiding precision subtyping and individualised therapy. Finally, we highlight key challenges and future directions in the clinical translation of tirzepatide pharmacogenomics, aiming to inform personalized, genomics-guided therapy for cardiometabolic disease. Full article

The use of exogenous enzymes in the nutrition of dairy cows is an innovative and efficient strategy to maximize productivity and milk quality, with positive applications in the economic and environmental aspects of dairy farming. Therefore, the objective of this study was to evaluate whether the addition of a blend of exogenous enzymes to the diet of lactating Jersey cows has a positive effect on productive performance, milk quality, animal health, ruminal environment, and digestibility. Twenty-one primiparous Jersey cows, with 210 days in lactation (DL), were used. The exogenous enzymes used were blends containing mainly protease, in addition to cellulase, xylanase, and beta-glucanase. The animals were divided into three groups with seven replicates per group (each animal being the experimental unit), as follows: Control (T-0), basal diet without enzyme addition; Treatment (T-80), animals fed enzymes in the diet at a daily dose of 80 mg per kg of dry matter (DM); Treatment (T-160), animals fed enzymes in the diet at a daily dose of 160 mg per kg of DM. The study lasted 84 days, during which higher milk production was observed in the treated groups (T-80 and T-160) compared to the control group (p = 0.04). When calculating feed efficiency from days 1 to 84, greater efficiency was observed in both groups that received the blend compared to the control (p = 0.05). In the centesimal composition of the milk, it was observed that the percentage of protein in the milk of the T-160 group was higher compared to the control group (p = 0.03). The effect of the enzymes was verified for butyric (p = 0.05) and palmitic (p = 0.05) fatty acids. We also observed the effect of the enzyme blend on the amount of volatile fatty acids (VFAs), which were higher in the ruminal fluid of cows that received the enzymes (p = 0.01). Cows that consumed enzymes showed a higher apparent digestibility coefficient of crude protein (p = 0.01). In vitro, the main result is related to lower gas production in 24 and 48 h at T-160. We concluded that the use of a blend of exogenous enzymes in the diet of lactating Jersey cows was able to increase milk production in these animals, resulting in greater feed efficiency and also an increase in milk protein content, positively modulating the fatty acid profile in the rumen and improving the apparent digestibility of nutrients. Full article

Background and Objectives: This study evaluated the correlation between hyperferritinemia and markers of liver steatosis, fibrosis, and risk of liver-related events in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Material and Methods: This study included 271 patients that underwent a comprehensive medical evaluation. Hyperferritinemia was defined by values >200 ng/mL (females) and >300 ng/mL (males). Liver fibrosis and steatosis were evaluated by several non-invasive indexes, and Liver Risk Score (LRS) was calculated to determine the risk of liver-related events. Their correlation with serum ferritin was investigated by bivariate and multiple regression analyses. Receiver Operating Characteristic (ROC) analyses were used to assess the accuracy to predict advanced fibrosis and increased LRS. Statistical significance was set at p < 0.05. Results: The median serum ferritin level was 94.4 [128.1] ng/mL. Metabolic hyperferritinemia was present in 12.54% of patients. Patients with hyperferritinemia had higher liver enzymes, HbA1c, HOMA-IR, and increased markers of liver steatosis and fibrosis, with a higher prevalence of advanced fibrosis (OR = 3.744 [1.481, 9.460], p = 0.0081). LRS was highest in patients with hyperferritinemia (7.99 ± 2.01 vs. 7.12 ± 1.32 vs. 6.54 ± 1.06, p < 0.0001). Serum ferritin levels were correlated with LRS (β = 0.190 [0.001; 0.003], p < 0.001), liver fibrosis (Fibrotic NASH Index) (β = 0.198 [0.000; 0.001], p < 0.001), and steatosis, while haptoglobin concentrations were correlated negatively with them. Serum ferritin predicted the moderate risk of liver-related outcomes with an acceptable performance (area under the ROC curve = 0.726 [0.590; 0.862], p = 0.001). Conclusions: Hyperferritinemia is associated with liver fibrosis and steatosis and a higher risk of liver-related events in patients with T2DM and MASLD. Full article

Background: Ustekinumab (UST) is a monoclonal antibody (mAb) used in the treatment of inflammatory bowel disease (IBD). Elevated serum concentrations are typically associated with improved therapeutic outcomes, and therapeutic drug monitoring (TDM) is a useful tool for guiding mAbs treatment. This study aimed to develop a dried blood spot (DBS) method for TDM of UST in patients with IBD. Methods: The commercial enzyme-linked immunosorbent assay for plasma samples was optimized for DBS samples and subsequently validated according to international guidelines for classical and DBS-specific validation parameters. It was then applied to analyze serum and DBS samples obtained from venous and capillary blood of IBD patients undergoing UST therapy. Results: The method was linear (3–12 mg/L) with acceptable inter-day accuracy (90.1–106%) and precision (<12%). We confirmed that there was no hematocrit effect and that DBS samples were stable for one month under room conditions. A linear model was developed between venous DBS and serum UST concentrations, which showed no systemic bias, and 71% of the samples were within ±20% of the mean. In addition, a linear correlation between venous DBS and capillary DBS samples was established, showing no significant bias, with 84% of samples within ±20% of the mean. Finally, a novel strategy was developed to overcome the limitations of poor-quality samples (irregular shapes) based on area image analysis. Conclusions: The newly developed DBS method is the first to enable reliable measurement of UST in capillary blood, appropriate clinical interpretation of the measured concentrations, and remote monitoring of patients in the early phase of therapy. Full article

Type II diabetes mellitus (T2DM) is characterized by chronic glycolipid metabolic dysregulation. This study aimed to investigate the effects and mechanisms of Artemisia integrifolia Linn. (LH) as a functional food in a T2DM rat model. The UPLC-Q-TOF-MS/MS technique was used to identify the components of LH. T2DM was induced in rats via a high-fat/high-sugar diet combined with streptozotocin (STZ, 35 mg/kg, i.p.). The rats were subsequently treated with LH (90 mg/kg, 180 mg/kg) for 15 days. A total of 66 compounds were identified in both positive and negative ions. LH treatment resulted in an increase in body weight while reducing FBG levels. It also improved insulin resistance, blood lipid levels, liver pathology, function, and lipid accumulation. Furthermore, 18 metabolites and 5 metabolic pathways were identified in the liver. Mechanistically, LH may improve T2DM through modulation of the S1P and PI3K/AKT signaling pathway. Caffeic acid, coumarin, trifolin, and apigetrin were identified as the likely active components. In conclusion, LH may mitigate glycolipid metabolism disorders in T2DM rats by modulating metabolic profiling, S1P, and the PI3K/AKT signaling pathway, supporting its potential as a functional food. Full article

Objectives: We investigated the relationship between bone metabolic markers or bone mineral density (BMD) and sarcopenia in patients with type 2 diabetes mellitus (T2DM). Methods: In this cross-sectional study involving 119 subjects (76 women and 43 men), bone metabolic markers were evaluated by bone alkaline phosphatase and bone tartrate-resistant acid phosphatase (TRACP-5b). BMD was measured using the dual-energy X-ray absorptiometry method, and sarcopenia was diagnosed using skeletal muscle mass index (SMI), evaluated by body composition measurement and handgrip strength. Results: Significant correlation was observed between handgrip strength or SMI and TRACP-5b in both sexes (correlation coefficients were −0.50 in handgrip strength and −0.41 in SMI in men; −0.25 in handgrip strength and −0.21 in SMI in women). Furthermore, significant correlation was observed between handgrip strength or SMI and BMD of the femoral neck in both sexes (correlation coefficients were 0.33 in handgrip strength and 0.44 in SMI in men; 0.34 in handgrip strength and 0.47 in SMI in women). The concentrations of TRACP-5b with sarcopenia were significantly higher than those without (643.8 ± 261.9 vs. 455.7 ± 165.6 mU/dL), and BMD of femoral neck with sarcopenia was significantly lower than those without (0.54 ± 0.12 vs. 0.66 ± 0.16 g/cm²). TRACP-5b (odds ratio 1.05, 95% confidence interval 1.01–1.10) and femoral neck BMD (odds ratio 0.30, 95% confidence interval 0.14–0.68) were associated with the presence of sarcopenia after adjustment for confounders. Conclusions: TRACP-5b and BMD of the femoral neck were associated with sarcopenia in patients with T2DM. Full article

Background and Objectives: Type 2 diabetes (T2DM) substantially increases cardiovascular risk; beyond the well-recognized left-ventricular involvement in diabetic cardiomyopathy, emerging data indicate subclinical right-ventricular (RV) dysfunction may also be present. This study aimed to evaluate whether speckle-tracking echocardiography identifies subclinical right-ventricular systolic dysfunction in type 2 diabetes, despite normal conventional indices and preserved global systolic function. Materials and Methods: We conducted a cross-sectional, single-center study in accordance with STROBE recommendations, enrolling 77 participants, 36 adults with T2DM, and 41 non-diabetic controls, between December 2024 and July 2025. All participants underwent comprehensive transthoracic echocardiography, including conventional parameters (tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TV S’), right ventricular fractional area change (RVFAC)) and deformation imaging (right ventricular global longitudinal strain (RV GLS), right ventricular free wall longitudinal strain (RVFWS)) using speckle-tracking echocardiography. Biochemical and clinical data, including glycosylated hemoglobin (HbA1c), were recorded. Correlation and ROC curve analyses were performed to explore associations and predictive value. Results: The mean age was comparable between the two groups (62.08 ± 9.54 years vs. 60.22 ± 13.39 years; p = 0.480). While conventional RV parameters did not differ significantly between groups, diabetic patients had significantly lower RV GLS (−13.86 ± 6.07% vs. −18.59 ± 2.27%, p < 0.001) and RVFWS (−15.64 ± 4.30% vs. −19.03 ± 3.53%, p < 0.001). HbA1c levels correlated positively with RV strain impairment (RVFWS r = 0.41, p < 0.001). Both RV GLS and RVFWS were independent predictors of RV dysfunction in logistic regression analysis. ROC analysis showed good diagnostic performance for RV GLS, AUC = 0.84 with an optimal cut-off −17.2% (sensitivity 86.1% and specificity 80.5%) and RVFWS, AUC = 0.76 with cut-off −17.6% (sensitivity 77.8; specificity 80.5%) in identifying early myocardial involvement. Conclusions: RV systolic dysfunction may occur early in T2DM, even when traditional echocardiographic indices remain within normal limits. Speckle-tracking echocardiography, particularly RV GLS and RVFWS, offers sensitive detection of subclinical myocardial impairment, reinforcing its value in early cardiovascular risk stratification among diabetic patients. Full article

Aim: To investigate the synergistic effects of exercise training and Brassica oleracea var. italica (broccoli sprout) supplementation on Apolipoprotein A-I, B-100, and J levels in men with Type 2 diabetes mellitus (T2DM). Methods: Forty-four males with T2DM were randomly assigned to four groups: Control (CG), Supplement (SG), Training (TG), and Training + Supplement (TSG) groups. Participants in the supplement groups (SG and TSG) received 10 g of broccoli supplement after meals for 12 weeks, while those in the training groups (TG and TSG) participated in a structured exercise program (resistance and aerobic), performed three times per week for 12 weeks, at intensities of 60–70% one-repetition maximum (1RM) for resistance training and 60–70% peak oxygen uptake (VO_2peak) for aerobic training. Results: Circulating levels of apolipoproteins improved after 12 weeks in the TSG, TG, and SG groups. However, the TSG group exhibited the most pronounced improvements across metabolic and lipoprotein markers, reflecting an additive effect of both interventions. Specifically, the TSG group demonstrated absolute reductions in ApoB-100 (−48.30 ± 7.20 mg/dL) and ApoJ (−44.05 ± 5.76 mg/dL), along with an increase in ApoA-I (+44.92 ± 6.05 mg/dL). Main effect analysis revealed that exercise training elicited the most substantial improvements across metabolic and lipoprotein markers, with large effect sizes for glucose (η²p = 0.787), insulin (η²p = 0.640), HOMA-IR (η²p = 0.856), ApoA-I (η²p = 0.685), ApoB-100 (η²p = 0.774), ApoJ (η²p = 0.848), and HDL-C (η²p = 0.535). Supplementation showed moderate effects, particularly on HOMA-IR (η²p = 0.370), ApoA-I (η²p = 0.383), and ApoB-100 (η²p = 0.334), supporting an additive but exercise-dominant benefit. The combined intervention group (TSG) showed the most pronounced improvements across all measured outcomes, with large effect sizes for ApoA-I (η²p = 0.883), glucose (η²p = 0.946), insulin (η²p = 0.881), HOMA-IR (η²p = 0.904), and ApoJ (η²p = 0.852). Conclusions: The effects of combining training and broccoli sprout supplementation on apolipoprotein levels are likely to result from the activation of two separate pathways, one from training and the other from supplementation. This dual-modality intervention could serve as an effective complementary strategy in managing metabolic and cardiovascular risk factors for individuals with T2DM. However, the magnitude of change induced by the combination of exercise training and broccoli supplementation was largely driven by the training component, with supplementation providing complementary but less consistent benefits. Full article

Background: Dicarbonyls and advanced glycation end-products (AGEs) contribute to oxidative stress, inflammation, and complications in type 2 diabetes mellitus (T2DM). Menaquinone-7 (MK-7), a vitamin K2 subtype, has shown benefits for glucose tolerance and vascular health in some studies. We evaluated the impact of MK-7 on dicarbonyls, free AGEs, and protein nitration/oxidation adducts in a rat model of T2DM. Methods: Male heterozygous (fa/+, control) and homozygous (fa/fa, diabetic) Zucker Diabetic Fatty rats were fed a diabetogenic diet without or with MK-7 for 12 weeks. After sacrifice, plasma dicarbonyls as well as plasma and urinary levels of free AGEs and protein nitration/oxidation adducts were quantified by isotope dilution tandem mass spectrometry. Results: Diabetic rats showed significantly increased plasma glyoxal, 3-deoxyglucosone, and fructosyl-lysine with non-significant trends toward increased methylglyoxal-derived hydroimidazolone and methionine sulfoxide, as well as reductions in methylglyoxal and dityrosine. Urinary carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine (all significant), and dityrosine (non-significant) were elevated in diabetic rats; glucosepane (non-significant) was reduced. MK-7 supplementation reduced no measured parameter but was associated with non-significant further increases in plasma glyoxal-derived hydroimidazolone, carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine, 3-nitrotyrosine, and methionine sulfoxide, as well as in urinary glyoxal-derived hydroimidazolone, carboxyethyl-lysine, fructosyl-lysine, and 3-nitrotyrosine, in diabetic rats. Correlation analysis revealed significant associations between glucose, dicarbonyls, AGEs, and oxidative markers. Conclusions: High-dose MK-7 supplementation did not improve dicarbonyl stress, AGE burden, or protein nitration/oxidation. With respect to available scientific evidence and our observations, the combination of glycemia-driven amplification of glycation and oxidative stress, as well as MK-7-induced glutathione depletion, were likely causative. Full article

Background/Objectives: Diabetes mellitus (DM) is an increasingly prevalent endocrine disorder affecting humans and companion animals. Type 1 DM (T1DM) and type 2 DM (T2DM) are well characterized in humans, and canine DM most often resembles T1DM, marked by insulin dependence and β-cell destruction. Conversely, feline DM shares key features with human T2DM, including insulin resistance, obesity-related inflammation, and islet amyloidosis. This review provides a comprehensive comparative analysis of antidiabetic therapies in humans, dogs, and cats, focusing on three core areas: disease pathophysiology, pharmacological and delivery strategies, and translational implications. In human medicine, a wide array of insulin analogs, oral hypoglycemic agents, and incretin-based therapies, including glucagon-like peptide-1 receptor agonists (liraglutide) and sodium-glucose cotransporter-2 inhibitors (empagliflozin), are available. Veterinary treatments remain limited to species-adapted insulin formulations and off-label use of human drugs. Interspecies differences in gastrointestinal physiology, drug metabolism, and behavioral compliance influence therapeutic efficacy and pharmacokinetics. Recent innovations, such as microneedle patches for insulin delivery and continuous glucose monitoring systems, show promise in humans and animals. Companion animals with naturally occurring diabetes serve as valuable models for preclinical testing of novel delivery platforms and long-acting formulations under real-world settings. While these technologies show potential, challenges remain in regulatory approval and behavioral adaptation in animals. Conclusions: Future research should prioritize pharmacokinetic bridging studies, veterinary-specific formulation trials, and device validation in animal models. By highlighting shared and species-specific characteristics of DM pathogenesis and treatment, this review advocates a One Health approach toward optimized antidiabetic therapies that benefit human and veterinary medicine. Full article

Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) are chronic disorders characterized by hyperglycemia. Sechium edule (S. edule) has emerged as a complementary option due to its bioactive compounds. A systematic review of preclinical and clinical studies was carried out until 25 May 2025 in the databases PubMed, Scopus, Web of Science, SciELO, and TESIUNAM. The keywords were “diabetes mellitus”, “Sechium edule”, “Squash”, “Chayote”, “hypoglycemic effect”, and “Older adults”. A total of 110 articles were found; 11 met eligibility criteria (six clinical trials and five preclinical trials). Three clinical trials met the requirements for meta-analysis. The mean difference (MD) was calculated, and data were analyzed using RevMan 5.4 software. The meta-analysis showed a statistically significant decrease in serum glucose after three months (MD = −20.56, 95% CI −29.35 to −11.77, p < 0.0001) and six months after intervention (MD = −12.96, 95% CI = −21.90 to −4.02, p = 0.004). Likewise, there was a significant decrease in glycosylated hemoglobin (HbA1c) after three months (MD = −1.12, 95% CI = −1.45, −0.78, p < 0.0001) and after six months of intervention (MD = −0.92, 95% CI = −1.13, −0.25, p = 0.002). Our findings showed that S. edule intake has a statistically significant hypoglycemic effect in older adults with T2DM or MS by decreasing serum glucose and HbA1c levels. However, the magnitude of the decrease is clinically modest, so it cannot be a substitute for pharmacological treatment. For this reason, the intake of S. edule can only be considered as a complement to pharmacological treatment. Full article

Obesity (lipotoxicity) results from a chronic imbalance between energy intake and expenditure. It is strongly associated with type 2 diabetes mellitus (T2DM, glucotoxicity) and considered a major risk factor for the development of metabolic complications. Their convergence constitutes “diabesity”, representing a major challenge for public health worldwide. Limited treatment efficacy highlights the need for novel, multi-targeted therapies. Non-shivering thermogenesis (NST), mediated by brown and beige adipose tissue and skeletal muscle, has emerged as a promising therapy due to its capacity to increase energy expenditure and improve metabolic health. Also, skeletal muscle plays a central role in glucose uptake and lipid oxidation, further highlighting its relevance in diabesity. This review explores current and emerging knowledge on physiological stimuli, including cold exposure, physical activity, and fasting, as well as bioactive ingredients and drugs that stimulate NST in thermogenic tissues. Special emphasis is placed on melatonin as a potential regulator of mitochondrial function and energy balance. The literature search was conducted using MEDLINE and Web of Science. Studies were selected based on scientific relevance, novelty, and mechanistic insight; prioritizing human and high-quality rodent research published in peer-reviewed journals. Evidence shows that multiple interventions enhance NST, leading to improved glucose metabolism, reduced fat accumulation, and increased energy expenditure in humans and/or rodents. Melatonin, in particular, shows promise in modulating thermogenesis through organelle-molecular pathways and mitochondrial protective effects. In conclusion, a multi-target approach through the activation of NST by physiological, nutritional, and pharmacological agents offers an effective and safe treatment for diabesity. Further research is needed to confirm these effects in clinical practice and support their use as effective therapeutic strategies. Full article