To evaluate the effects of a very-low-calorie diet (VLCD) on insulin resistance (IR), metabolic gene expression, and fatty acid profiles in obese patients (body mass index [BMI] ≥ 30 kg/m2) undergoing bariatric surgery compared to age- and sex-matched nonobese controls (BMI ≤ 25 kg/m2) undergoing elective abdominal surgery.

A total of 38 participants (21 obese and 17 nonobese controls) were recruited for this study. Obese patients underwent VLCD (800 kcal/day) for four weeks before surgery. Fasting blood samples and tissue biopsies were collected during surgery. Key parameters included IR (measured using HOMA-IR), metabolic gene expression (quantified via RT-PCR), and fatty acid composition (analyzed by gas chromatography). Data were compared between pre- and post-VLCD groups in the obese cohort.

GLUT4 expression was reduced (1.57-fold, p = 0.025), whereas PDK4 (3.9-fold, p = 0.002), CPT1 (2.5-fold, p = 0.013), and AMPK (twofold, p = 0.004) expression were Correlation analysis revealed that GLUT4 was negatively correlated with BMI (r = -0.85), glucose (r = -0.94), and IR (r = -0.79), CPT1 was positively correlated with these parameters (BMI: r = 0.84, glucose: r = 0.92, IR: r = 0.82). VLCD significantly reduced monounsaturated fatty acids, including alpha-linolenic acid (p = 0.03) and erucic acid (p = 0.019). Postsurgical improvements included reductions in BMI (Δ = 6.21, p < 0.0001), glucose level (Δ = 6.94, p = 0.0007), and IR (Δ = 10.19, p = 0.0039).

VLCD modulated metabolic gene expression and fatty acid profiles, enhancing IR and metabolic health both pre- and post-surgery. This represents a critical strategy for optimizing the outcomes of obese patients undergoing bariatric surgery.

The online version contains supplementary material available at 10.1007/s40200-025-01625-5.

Cage rearing is a promising farming method. However, our previous studies have demonstrated that changes in farming practices induce oxidative stress and inflammation in the liver and duodenum of ducks. Resveratrol (RES), a natural plant polyphenol, possesses antioxidant, anti-inflammatory, and cytoprotective properties. This study evaluated the alleviating effects of RES against cage-rearing-induced duck health problems, emphasizing the involvement of redox imbalance, inflammatory response, endoplasmic reticulum (ER) stress, apoptosis, and PI3K/AKT and MAPK/ERK pathways. A total of 120 healthy 12-week-old female ducks were transferred to a cage system and randomly assigned to two dietary RES groups with 6 replicates each (10 ducks per replicate), including basal diet + 0 mg/kg RES (control group, CON), and basal diet + 500 mg/kg RES (RES-treated group, RES). During the early stages (within 10 days) of cage rearing, blood, liver, and duodenal samples were collected for analysis. The results demonstrated that RES reduced histopathological damage in the liver and duodenum of cage-reared ducks. It also reduced serum albumin levels, increased serum aspartate aminotransferase and alanine aminotransferase levels, and enhanced antioxidant (increased CAT, GSH-Px, SOD, and T-AOC activities in the serum, liver, and duodenum, and reduced the increase in MDA) and anti-inflammatory properties (reduced pro-inflammatory cytokines interleukin (IL)-1β and IL-6 secretion and increased anti-inflammatory cytokine IL-4 levels). Additionally, quantitative real-time polymerase chain reaction revealed that RES intervention reversed the abnormal mRNA abundance of biomarkers associated with inflammatory injury (iNOS and COX2) in the liver, and ER stress (GRP78) and apoptosis (Bax and Bcl2) in the liver and duodenum of cage-reared ducks. Further analysis of key proteins in the PI3K/AKT and ERK MAPK signaling pathways revealed that RES promoted AKT phosphorylation in the liver and duodenum of cage-reared ducks and reduced cleaved caspase-3 protein content. Overall, RES prevents cage-rearing stimuli-induced liver and intestinal injury in ducks by enhancing liver function, improving antioxidant properties, inhibiting inflammation, ER stress, and apoptosis, and activating the PI3K/AKT signaling pathway.

Increasing evidence indicates resveratrol (RES) supplementation evokes anti-obesogenic responses that could mitigate obesity-induced reductions in skeletal muscle (SkM) contractility. Contractile function is a key facet of SkM health that underpins whole body health. For the first time, the present study examines the effects of a high-fat diet and RES supplementation on isolated soleus (SOL) and extensor digitorum longus (EDL) contractile function. Female CD-1 mice, ∼6 weeks old (n = 38), consumed a standard laboratory diet (SLD) or a high-fat diet (HFD), with or without RES (4 g kg-1 diet) for 12 weeks. SOL and EDL (n = 8-10 per muscle, per group) were isolated and then absolute and normalised (to muscle size and body mass) isometric force and work loop power output (PO) were measured, and fatigue resistance was determined. Furthermore, sirtuin-1 expression was determined to provide mechanistic insight into any potential contractile changes. For SOL absolute force was higher in HFDRES compared to HFD (P = 0.033), and PO normalised to body mass and cumulative work during fatigue were reduced in HFD groups (P < 0.014). EDL absolute and normalised PO and cumulative work during fatigue were lower in HFD compared to other groups (P < 0.019). RES negated most adverse effects of HFD consumption on EDL contractility, with HFDRES producing PO and cumulative work comparable to the SLD groups. Sirtuin-1 expression was not influenced by diet in either muscle (P > 0.165). This study uniquely demonstrates that RES attenuates HFD-induced reductions in contractile performance of EDL, but this response is not explained by altered sirtuin-1 expression. These results suggest RES may be an appropriate strategy to alleviate obesity-induced declines in SkM function. KEY POINTS: Skeletal muscle health, a precursor for disease prevention, whole body health and quality of life, is substantially reduced because of obesity. Growing evidence suggests that the anti-obesogenic effects of nutritional supplement resveratrol may mitigate against obesity-induced muscle pathology. However, the effect of resveratrol on skeletal muscle contractile performance, a primary marker of skeletal muscle health, is yet to be examined. Our findings indicate that resveratrol reduces the adverse effects of high-fat diet consumption on the contractile performance of isolated fast twitch muscle and reduces the accumulation of central adipose. Resveratrol had little effect on skeletal muscle performance of standard diet mice, highlighting its specific efficacy in addressing high-fat diet-induced muscle pathology.

The prevalence of lipid metabolism disorders, including obesity, increases with age in cats and humans. Obesity is a condition characterized by systemic low-grade inflammation and oxidative stress caused by excessive visceral fat accumulation. Resveratrol (RSV), a natural plant polyphenol, modulates the expression of anti-inflammatory factors. This study aimed to investigate the effects of resveratrol supplementation on lipid metabolism in both healthy and obese cats and assess its potential as a dietary supplement for improving lipid metabolism disorders in this population.

Plasma metabolite and hormone concentrations, and enzyme activities were measured in healthy, obese, and overweight cats supplemented with RSV for 4 weeks. RVS was supplemented at 1 mg/kg body weight/day (low dose) and 5 mg/kg/day (high dose) in capsules for 4 weeks.

Body weight, body condition score, BUN, and insulin concentrations did not change in obese or overweight cats with RSV supplementation for 4 weeks. Plasma triglyceride, free fatty acids, and serum amyloid A (SAA) concentrations and lactate dehydrogenase (LDH) activities decreased, and adiponectin concentrations increased markedly in obese and overweight cats after RSV supplementation.

Decreased plasma SAA concentrations and LDH activities and increased plasma adiponectin concentrations in obese and overweight cats seem to be induced by the improvement in liver function and the anti-inflammatory effect of RSV. Moreover, RSV supplementation may be useful in treating lipid metabolism disorders, including obesity, in cats.

6:2 chloro-polyfluorooctane ether sulfonate (F-53B) is considered neurotoxic, but its mechanisms remain unclear. This study aimed to investigate the toxic effects of F-53B on neuronal cells, focusing on the role of the V-ATPase-AMPK axis in the mechanism of abnormal energy metabolism. Mouse astrocytes (C8-D1A) and human neuroblastoma cells (SH-SY5Y) exposed to F-53B were used as in vitro models. Our findings demonstrated that F-53B inhibited the expression of V-ATPase B2 and reduced V-ATPase activity, leading to an increase in lysosomal pH, decreased expression of TRPML1, and lysosomal Ca2 + accumulation. In turn, led to reduced the expression of CaMKK2 and phosphorylated AMPK (p-AMPK). Ultimately, mitochondria were damaged, evidenced by increased mitochondrial reactive oxygen species, mitochondrial membrane potential, and impaired mitochondrial oxidative phosphorylation, as shown by reduced NDUFS1 expression and diminished respiratory chain complex I activity. F-53B reduced the expression of the key glycolytic protein PFKFB3. Notably, V-ATPase B2 overexpression indirectly activates AMPK. Furthermore, resveratrol, an AMPK agonist, alleviates mitochondrial dysfunction and increases ATP production by promoting the recovery of mitochondria and glycolytic pathways. These findings elucidate a novel mechanism by which F-53B induces neurotoxicity through the V-ATPase-AMPK axis, and indicate V-ATPase and AMPK as potential therapeutic targets.

The antidiabetic activity of the novel Buckwheat protein-derived peptide (Ala-Phe-Tyr-Arg-Trp, AFYRW) and its associated protein glycosylation have been verified. Our preliminary study demonstrates the potential of AFYRW as a therapeutic agent for diabetes, but the mechanism needs further investigation. Given the vital role of O-linked N-acetylglucosamine transferase (OGT) in diabetes mellitus and insulin resistance (IR), we focused on the underlying molecular mechanisms of them in ameliorating IR. We found AFYRW protects against hyperglycemia in diabetic mice and improves glucose metabolism in an IR cell model. Mechanistically, we demonstrated that AFYRW decreases glutamine-fructose-6-phosphate amidotransferase (GFAT) expression via X-box binding protein 1 (XBP1) in the hexosamine biosynthesis pathway (HBP), consequently decreasing OGT and stimulating the SIRT1/PGC1α pathway. Of note, the overlapping roles of increased SIRT1 and decreased OGT caused by AFYRW ameliorated IR. The data presented here show that AFYRW contributes to metabolism by directly controlling glucose homeostasis. Taken together, our study unveils that AFYRW protects against both insulin resistance and diabetes mellitus-induced hyperglycemia through OGT to regulate the SIRT1/PGC1α pathway, which provides a mechanistic basis for novel AFYRW to be a potential therapeutic agent.

Resveratrol (RES), a common type of plant polyphenols, has demonstrated promising therapeutic efficacy and safety in animal models of pancreatitis and pancreatic cancer. However, a comprehensive analysis of these data is currently unavailable. This study aimed to systematically review the preclinical evidence regarding RES's effects on animal models of pancreatitis and pancreatic cancer via meta-analyses and optimised machine learning techniques.

Animal studies published from inception until June 30th 2024, were systematically retrieved and manually filtrated across databases including PubMed, EMBASE, Web of Science, Ovid MEDLINE, Scopus, and Cochrane Library. Methodological quality of the included studies was evaluated following the SYRCLE's RoB tool. Predefined outcomes included histopathology and relevant biochemical parameters for acute pancreatitis, and tumour weight/tumour volume for pancreatic cancer, comparing treatment and model groups. Pooled effect sizes of the outcomes were calculated using STATA 17.0 software. Machine learning techniques were employed to predict the optimal usage and dosage of RES in pancreatitis models.

A total of 50 studies comprising 33 for acute pancreatitis, 1 chronic pancreatitis, and 16 for pancreatic cancer were included for data synthesis after screening 996 records. RES demonstrated significant improvements on pancreatic histopathology score, pancreatic function parameters (serum amylase and lipase), inflammatory markers (TNF-α, IL-1β, IL-6, and pancreatic myeloperoxidase), oxidative biomarkers (malondialdehyde and superoxide dismutase), and lung injury (lung histopathology and myeloperoxidase) in acute pancreatitis models. In pancreatic cancer models, RES notably reduced tumour weight and volume. Machine learning highlighted tree-structured Parzen estimator-optimised gradient boosted decision tree model as achieving the best performance, identifying course after disease induction, total dosage, single dosage, and total number of doses as critical factors for improving pancreatic histology. Optimal single dosage was 20-105 mg/kg with 3 to 9 doses.

This study comprehensively demonstrates the therapeutic effects of RES in mitigating pancreatitis and pancreatic cancer in animal models. Anti-inflammatory, anti-oxidative, and anti-tumour growth properties are potential mechanisms of action for RES.

Metabolic syndrome-related diseases frequently involve disturbances in skeletal muscle lipid metabolism. The accumulation of lipid metabolites, lipid-induced mitochondrial stress in skeletal muscle cells, as well as the inflammation of adjacent adipose tissue, are associated with the development of insulin resistance and metabolic dysfunction. Consequently, when antidiabetic medications are used to treat various chronic conditions related to hyperglycaemia, the impact on skeletal muscle lipid metabolism should not be overlooked. However, current research has predominantly focused on muscle mass rather than skeletal muscle lipid metabolism and its interplay with glucose metabolism. In this review, we summarised the latest research on the effects of antidiabetic drugs and certain natural compounds with antidiabetic activity on skeletal muscle lipid metabolism, focusing on data from preclinical to clinical studies. Given the widespread use of antidiabetic drugs, a better understanding of their effects on skeletal muscle lipid metabolism merits further attention in future research.

The characterization and antioxidant ability of Res-loaded MP-CS stabilized Pickering emulsion, and its effects of fat reduction (25%, 50%, 75%, and 100%) in meat patties on pH, color, texture, cooking yield and antioxidant activity were investigated. Fat substitute using emulsion had no significant effect on pH and cooking yield. The addition of emulsion increased L* value and reduced a* value. a* value of meat patties with resveratrol added were higher than those without resveratrol group. Hardness and chewiness of meat patties with 25% and 100% fat replacement was lower than 50% and 75% fat replacement. The addition of emulsion could improve the network structure of meat patties and enhance oxidative stability. Oxidative stability of meat patties was improved by Res-loaded MP-CS stabilized Pickering emulsion. The results showed that MP-CS stabilized Pickering emulsion had great potential to be used as fat substitute for developing low-fat meat products, and the addition of resveratrol can improve the antioxidant ability of substitute fat meat products.

Resveratrol, a natural polyphenol compound, possesses anti-aging, antitumor, and vascular protective properties. These attributes are believed to stem from its influence on Sirtuin 1 (Sirt1), a member of the human Sirtuin family and a nicotinamide adenine dinucleotide-dependent histone deacetylase.

The aim of this study was to quantitatively investigate the impact of resveratrol supplementation on Sirt1 levels in adults by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs) involving resveratrol supplementation.

This Grading of Recommendations Assessment, Development and Evaluation-assessed systematic review involved a comprehensive search of PubMed, Embase, MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar databases using related keywords and was conducted from March 14, 2024, to April 15, 2024, to identify all RCTs investigating resveratrol's effects on Sirt1. Effect sizes were quantified as mean differences (MDs) or standardized mean differences (SMDs), with standard deviations of outcomes. An overall effect estimate was derived using a random-effects model when 2 or more studies reported similar outcomes. Statistical heterogeneity was assessed through the calculation of I2 statistics. In addition, a dose-response analysis was performed to assess potential dose-response relationships. Risk of bias was assessed using the Cochrane risk-of-bias tool for RCTs (RoB 2). Publication bias was evaluated using Begg's test and a meta-regression using the year of publication as a moderator.

Eleven RCTs examining the effects of resveratrol on Sirt1 gene expression (4 RCTs), protein expression (5 RCTs), and serum levels (3 RCTs) were included in the meta-analysis. The results showed no significant impact of resveratrol on Sirt1 gene expression (SMD = 0.05; 95% CI -0.24 to 0.344; P = .73), protein expression (SMD = 0.3; 95% CI -0.15 to 0.77; P = .18), or serum levels (MD = -0.04; 95% CI -0.235 to 0.16; P = .7). However, subgroup analyses suggested a significant increase in Sirt1 gene expression in studies with an intervention duration of <12 weeks and evaluating blood tissue. Furthermore, the impact of resveratrol on Sirt1 appeared to be influenced by the dosage regimen, with a significant effect for intervention duration.

Study results indicate that resveratrol supplementation does not significantly influence human Sirt1 based on the overall meta-analysis. However, the dose-response analysis suggests that the effect of resveratrol on Sirt1 depends on the dosage regimen.

Metabolic syndrome (MetS) is a cluster of interrelated metabolic abnormalities that significantly elevate the risk of cardiovascular disease, obesity, and diabetes. Flavonoids, a diverse class of bioactive polyphenolic compounds found in plant-derived foods and beverages, have garnered increasing attention as potential therapeutic agents for improving metabolic health. This review provides a comprehensive analysis of the therapeutic effects of flavonoids in the context of the MetS, with a particular focus on their modulation of the AMP-activated protein kinase (AMPK) pathway. AMPK serves as a central regulator of cellular energy balance, glucose metabolism, and lipid homeostasis, making it a critical target for metabolic intervention. Through a systematic review of the literature up to April 2024, preclinical studies across various flavonoid subclasses, including flavonols, and flavan-3-ols, were analysed to elucidate their mechanistic roles in metabolic regulation. Many studies suggests that flavonoids enhance glycolipid metabolism by facilitating glucose transporter 4 (GLUT4) translocation and activating the AMPK pathway, thereby improving glycemic control in diabetes models. In obesity-related studies, flavonoids demonstrated significant inhibitory effects on lipid synthesis, reduced adipogenesis, and attenuated proinflammatory cytokine secretion via AMPK activation. These findings show the broad therapeutic potential of flavonoids in addressing the MetS and its associated disorders. While these preclinical insights highlight flavonoids as promising natural agents for metabolic health improvement, it is important to note that their excessive concentrations may disrupt these pathways, potentially leading to metabolic imbalance and cytotoxicity. Further studies and clinical trials are essential to determine optimal dosing regimens, formulations, and the long-term safety and efficacy of flavonoids. This review highlights the importance of flavonoids for natural interventions targeting MetS and its comorbidities, offering a foundation for future translational research.

Cardiovascular diseases (CVDs) are experiencing a rapid surge and are widely recognized as the leading cause of mortality in the current aging society. Given the multifactorial etiology of CVDs, understanding the intricate molecular and cellular mechanisms is imperative. Over the past 2 decades, many scientists have focused on Sirtuins, a family of nicotinamide adenine dinucleotide-dependent deacylases. Sirtuins are highly conserved across species, from yeasts to primates, and play a crucial role in linking aging and diseases. Sirtuins participate in nearly all key physiological and pathological processes, ranging from embryogenic development to stress response and aging. Abnormal expression and activity of Sirtuins exist in many aging-related diseases, while their activation has shown efficacy in mitigating these diseases (eg, CVDs). In terms of research, this field has maintained fast, sustained growth in recent years, from fundamental studies to clinical trials. In this review, we present a comprehensive, up-to-date discussion on the biological functions of Sirtuins and their roles in regulating cardiovascular biology and CVDs. Furthermore, we highlight the latest advancements in utilizing Sirtuin-activating compounds and nicotinamide adenine dinucleotide boosters as potential pharmacological targets for preventing and treating CVDs. The key unresolved issues in the field-from the chemicobiological regulation of Sirtuins to Sirtuin-targeted CVD investigations-are also discussed. This timely review could be critical in understanding the updated knowledge of Sirtuin biology in CVDs and facilitating the clinical accessibility of Sirtuin-targeting interventions.

Metabolic syndrome (MetS) and mild cognitive impairment (MCI) are interconnected conditions sharing common pathological pathways, such as inflammation and oxidative stress, leading to the concept of "metabolic-cognitive syndrome." This highlights their mutual influence and potential overlapping therapeutic strategies. Although lifestyle modifications remain essential, nutraceutical supplementation has emerged as a promising adjunct for the prevention and management of these preclinical conditions. This review examines clinical and translational evidence on commonly used nutraceuticals targeting shared pathophysiological mechanisms of MetS and MCI. By addressing inflammation, oxidative stress, and metabolic dysfunction, these supplements may offer a valuable approach to mitigating the progression and consequences of both conditions. Understanding their efficacy could provide practical tools to complement lifestyle changes, offering a more comprehensive strategy for managing metabolic-cognitive syndrome.

The long-term pathological state known as metabolic syndrome is characterized by hypertension, insulin resistance diabetes, abdominal obesity, and hyperlipidemia. Seeking healthcare strategies with fewer side effects, such as herbal remedies, is preferable in terms of mitigating the negative consequences of synthetic medications. Ziziphus lotus (L.) (Rhamnaceae) or wild jujube, commonly known as "Sedra," is one of the best choices as it contains a variety of phytochemicals and biologically active compounds. Several flavonoids and stilbenes have been recognized as the primary bioactive components in wild jujube, including rutin, hyperin, isoquercitrin, and resveratrol. These polyphenols are pharmacologically active and have broad-spectrum beneficial effects for reducing the risk factors associated with metabolic syndrome. They exhibit antioxidant and anti-inflammatory properties, regulate lipid metabolism, and possess antiobesity, antihypertensive, and antidiabetic characteristics. However, there are certain limitations to their therapeutic application, such as low bioavailability. Various strategies have been proposed to enhance their pharmacokinetic profile and therapeutic potential for future use. The main goal of this review is to explore the underlying mechanisms related to the therapeutic effects of wild jujube and its active compounds in the treatment and prevention of metabolic syndrome.

Diabetes and obesity are globally prevalent metabolic disorders posing significant public health challenges. The effective management of these conditions requires integrated and personalized strategies. This study conducted a systematic literature review, identifying 335 relevant papers, with 129 core articles selected after screening for duplicates and irrelevant studies. The focus of the study is on the synergistic roles of functional foods, microbiotics, and nutrigenomics. Functional foods, including phytochemicals (e.g., polyphenols and dietary fibers), zoochemicals (e.g., essential fatty acids), and bioactive compounds from macrofungi, exhibit significant potential in enhancing insulin sensitivity, regulating lipid metabolism, reducing inflammatory responses, and improving antioxidant capacity. Additionally, the critical role of gut microbiota in metabolic health is highlighted, as its interaction with functional foods facilitates the modulation of metabolic pathways. Nutrigenomics, encompassing nutrigenetics and genomics, reveals how genetic variations (e.g., single-nucleotide polymorphisms (SNPs)) influence dietary responses and gene expression, forming a feedback loop between dietary habits, genetic variations, gut microbiota, and metabolic health. This review integrates functional foods, gut microbiota, and genetic insights to propose comprehensive and sustainable personalized nutrition interventions, offering novel perspectives for preventing and managing type 2 diabetes and obesity. Future clinical studies are warranted to validate the long-term efficacy and safety of these strategies.

Diabetes mellitus (DM) ranks among the most prevalent chronic metabolic diseases, characterized primarily by a persistent elevation in blood glucose levels. This condition typically stems from either insufficient insulin secretion or a functional defect in the insulin itself. Clinically, diabetes is primarily classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), with T2DM comprising nearly 90% of all diagnosed cases. Notably, the global incidence of T2DM has surged dramatically over recent decades. The adenylate-activated protein kinase (AMPK) signaling pathway is crucial in regulating cellular energy metabolism, marking it as a significant therapeutic target for diabetes and related complications. Natural products, characterized by their diverse origins, multifaceted bioactivities, and relative safety, hold considerable promise in modulating the AMPK pathway. This review article explores the advances in research on natural products that target the AMPK signaling pathway, aiming to inform the development of innovative antidiabetic therapies.

This study investigates the cardioprotective effects of intense caloric restriction (ICR) from birth in ovariectomized rats, a model of estrogen deficiency mimicking menopause. Our findings demonstrate that ICR significantly improved both basal and post-ischemic cardiac function, even in the absence of estrogens. The restricted animals exhibited enhanced cardiac contractility and relaxation, particularly after ischemia/reperfusion (I/R) injury, with superior functional recovery compared to control groups. Notably, ICR reduced key cardiometabolic risk factors, including blood pressure, heart rate, and adiposity, while improving glucose tolerance and insulin sensitivity. Additionally, while mitochondrial biogenesis remained unaffected, ICR preserved mitochondrial integrity by reducing the number of damaged mitochondria. This was linked to a reduction in oxidative stress, as evidenced by lower reactive oxygen species (ROS) production in the hearts of restricted animals. These results suggest that ICR offers a protective effect against cardiovascular dysfunction induced by estrogen depletion, potentially through enhanced antioxidant defenses and mitochondrial protection.

Resveratrol, a polyphenolic compound known for its diverse biological activities, has demonstrated multiple pharmacological effects, including anti-inflammatory, anti-aging, anti-diabetic, anti-cancer, and cardiovascular protective properties. Recent studies suggest that these effects are partly mediated through the regulation of macrophage polarization, wherein macrophages differentiate into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Our review highlights how resveratrol modulates macrophage polarization through various signaling pathways to achieve therapeutic effects. For example, resveratrol can activate the senescence-associated secretory phenotype (SASP) pathway and inhibit the signal transducer and activator of transcription (STAT3) and sphingosine-1-phosphate (S1P)-YAP signaling axes, promoting M1 polarization or suppressing M2 polarization, thereby inhibiting tumor growth. Conversely, it can promote M2 polarization or suppress M1 polarization by inhibiting the NF-κB signaling pathway or activating the PI3K/Akt and AMP-activated protein kinase (AMPK) pathways, thus alleviating inflammatory responses. Notably, the effect of resveratrol on macrophage polarization is concentration-dependent; moderate concentrations tend to promote M1 polarization, while higher concentrations may favor M2 polarization. This concentration dependence offers new perspectives for clinical treatment but also underscores the necessity for precise dosage control when using resveratrol. In summary, resveratrol exhibits significant potential in regulating macrophage polarization and treating related diseases.

Oxidative stress (OS) refers to the production of a substantial amount of reactive oxygen species (ROS), leading to cellular and organ damage. This imbalance between oxidant and antioxidant activity contributes to various diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative conditions. The body's antioxidant system, mediated by various signaling pathways, includes the AMPK-SIRT1-FOXO pathway. In oxidative stress conditions, AMPK, an energy sensor, activates SIRT1, which in turn stimulates the FOXO transcription factor. This cascade enhances mitochondrial function, reduces mitochondrial damage, and mitigates OS-induced cellular injury. This review provides a comprehensive analysis of the biological roles, regulatory mechanisms, and functions of the AMPK-SIRT1-FOXO pathway in diseases influenced by OS, offering new insights and methods for understanding OS pathogenesis and its therapeutic approaches.

Resveratrol (RES), a natural polyphenolic compound, has shown promise in enhancing skeletal muscle regeneration and metabolic function. This study aims to explore the impact of RES on muscle regeneration after injury through the regulation of antioxidant capacity and mitochondrial biogenesis. RES treatment significantly increased the ratio of tibialis anterior muscle mass to body weight, alongside reduced fasting glucose levels. Following cardiotoxin-induced injury, RES treatment improved muscle regeneration, characterized by greater formation of new fibers and better structural repair compared to the control. Notably, gene expression analyses demonstrated that RES-treated mice exhibited elevated levels of myogenic markers, such as paired box 7 (Pax7), myogenic factor 5 (Myf5), myoblast determination protein (MyoD), and Myogenin (MyoG). Concurrently, yes-associated protein (YAP) increased, underscoring its role in regulating satellite cell activity. Transcriptomic analysis identified enriched pathways related to muscle regeneration and mitochondrial biogenesis, with increased expression of mitochondrial transcription factors and higher mitochondrial DNA content in RES-treated mice. Furthermore, RES enhanced antioxidant capacity via the Kelch-like ECH-associated protein 1 (KEAP-1)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway, as indicated by elevated activities of total antioxidant capacity, Glutathione peroxidase (GSH-PX), and superoxidase dismutase (SOD). Collectively, these findings suggest that RES not only promotes muscle regeneration but also supports mitochondrial function and antioxidant defenses, positioning it as a food-derived pharmaceutical for targeting muscle repair after injury.

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, pose significant health challenges and economic burdens worldwide. Recent studies have emphasized the potential therapeutic value of activating silent information regulator-1 (SIRT1) in treating these conditions. Resveratrol, a compound known for its ability to potently activate SIRT1, has demonstrated promising neuroprotective effects by targeting the underlying mechanisms of neurodegeneration. In this review, we delve into the crucial role of resveratrol-mediated SIRT1 upregulation in improving neurodegenerative diseases. The role of the activation of SIRT1 by resveratrol was reviewed. Moreover, network pharmacology was used to elucidate the possible mechanisms of resveratrol in these diseases. Activation of SIRT1 by resveratrol had positive effects on neuronal function and survival and alleviated the hallmark features of these diseases, such as protein aggregation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. In terms of network pharmacology, the signaling pathways by which resveratrol protects against different neurodegenerative diseases were slightly different. Although the precise mechanisms underlying the neuroprotective effects of resveratrol and SIRT1 activation remain under investigation, these findings offer valuable insights into potential therapeutic strategies for neurodegenerative diseases.

Pterostilbene, a polyphenolic compound and an analog of resveratrol, exerts various biological activities and has higher bioavailability and metabolic stability than resveratrol. However, the effectiveness of pterostilbene intake in humans, particularly its effect on blood microRNA (miRNA) expression levels, has not been evaluated. Accordingly, this pilot study aimed to investigate the effects of pterostilbene on blood biochemistry and blood miRNA expression levels and the safety of continuous intake at doses of 10 or 100 mg/d over 12 wk. A double-blind, placebo-controlled parallel-arm comparison trial was conducted with 30 healthy men. In the analysis of blood miRNA expression levels, miR-34a and miR-193b showed very high increases at week 4 and after week 4 of intake, respectively, suggesting that the responders might be present among participants in the pterostilbene intake group. No adverse events were reported during the trial in any participant, and no abnormalities were observed upon examination by the responsible physician. Thus, pterostilbene intake would regulate blood miRNA expression levels, and the results can be utilized in human studies investigating miRNA expression levels with functional food ingredients.

Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.

Diabetes mellitus is a chronic metabolic disorder marked by hyperglycemia, resistance to insulin, and impaired function of the pancreatic β-cells; it advances into more serious complications like nephropathy, neuropathy, cardiovascular disease, and retinopathy; herbal medicine has indicated promise in not just mitigating the symptoms but also in managing the complications. This review would aim to evaluate the pharmacological aspect of the botanical therapies Anacardium occidentale, Allium sativum, Urtica dioica, and Cinnamomum zeylanicum, as well as their bioactive phytochemicals, quercetin, resveratrol, berberine, and epigallocatechin gallate (EGCG). In this review, we discuss their mechanisms for secreting the insulin sensitizers, carbohydrate-hydrolyzing enzymes, reduction in oxidative stress and effectiveness against diabetic complications-all through sensitivity to insulin. Great emphasis is laid on the integration of multi-omics technologies such as genomics, proteomics, metabolomics, and transcriptomics in the discovery of bioactive compounds. The nature of the technologies can evaluate the intrinsic complexities of herbal pharmacology and even identify therapeutic candidates. Finally, the review refers to the meagre clinical trials on the efficiency of these compounds in the metabolism of humans. High-quality future research, such as human large-scale trials, would be emphasized; improvement in the clinical validity of a drug might come from improved study design, better selection of potentially usable biomarkers, and enhanced safety profiles to guarantee efficacy with lessened risks.

Persicaria perfoliata (L.) is an herbaceous medicinal plant belonging to the Polygonaceae family. The plant is distributed in Nepal, India, Japan, China, Russia, and Korea. The present study involved the analysis of plant secondary metabolites, synthesis of silver nanoparticles (Ag NPs) using the plant, characterization, and exploration of antioxidant, antidiabetic, antibacterial, and cytotoxic activities. Among six different solvent extracts, the methanol extract displayed the highest total phenolic content (TPC) and total flavonoid content (TFC) of 68.61 ± 0.57 mg GAE/g and 40.69 ± 5.0 mg QE/g respectively. Ag NPs and hexane extract displayed the potential antioxidant activity of IC50 69.40 ± 0.13 and 144.50 ± 1.36 μg/mL in the DPPH assay. The α-amylase inhibition shown by an aqueous extract and the synthesized Ag NPs IC50 of 1188.83 ± 33.52 and 1369.30 ± 46.86 μg/mL respectively. In antibacterial activity, the highest ZOI of 16 mm was displayed by Ag NPs against Klebsiella pneumoniae followed by a ZOI of 11 mm for methanol extract against Shigella sonnei. Similarly, the lowest MIC and MBC of 0.78125 and 1.5625 mg/mL were recorded for both Ag NPs and methanol extract against Staphylococcus aureus. Aqueous extract and Ag NPs did not display significant toxicity against brine shrimp nauplii. Ag NPs displayed an IC50 of 251.86 ± 58.90 μg/mL against HeLa cell lines. Biosynthesized Ag NPs showed a distinct peak at 409 nm in UV-visible spectra. FTIR analysis revealed the involvement of different functional groups of the organic compounds present in plant extract as reducing, capping, and stabilizing agents in the synthesis of Ag NPs. XRD analysis confirmed the crystal structure of Ag NPs, whereas the average grain size of 44.28 nm was determined by FE-SEM analysis. EDX spectra established the elemental composition of Ag NPs. The present study shows the synthesized Ag NPs using plant extract impart the potential biological activities as compared to that of the crude extract.

Longevity medicine is an emerging and iterative healthcare discipline focusing on early detection, preventive measures, and personalized approaches that aim to extend healthy lifespan and promote healthy aging. This comprehensive review introduces the innovative concept of the "Longevity Pyramid." This conceptual framework delineates progressive intervention levels, providing a structured approach to understanding the diverse strategies available in longevity medicine. At the base of the Longevity Pyramid lies the level of prevention, emphasizing early detection strategies and advanced diagnostics or timely identification of potential health issues. Moving upwards, the next step involves lifestyle modifications, health-promoting behaviors, and proactive measures to delay the onset of age-related conditions. The Longevity Pyramid further explores the vast range of personalized interventions, highlighting the importance of tailoring medical approaches based on genetic predispositions, lifestyle factors, and unique health profiles, thereby optimizing interventions for maximal efficacy. These interventions aim to extend lifespan and reduce the impact and severity of age-related conditions, ensuring that additional years are characterized by vitality and wellbeing. By outlining these progressive levels of intervention, this review offers valuable insights into the evolving field of longevity medicine. This structured framework guides researchers and practitioners toward a nuanced strategic approach to advancing the science and practice of healthy aging.

Obesity is one of the world's major public health challenges. Its pathogenesis and comorbid metabolic disorders share common mechanisms, such as mitochondrial or endoplasmic reticulum dysfunction or oxidative stress, gut dysbiosis, chronic inflammation and altered autophagy. Numerous pro-autophagy dietary interventions are being investigated for their potential obesity-preventing or therapeutic effects. We summarize current data on the relationship between autophagy and obesity, and discuss various dietary interventions as regulators of autophagy-related genes in the prevention and ultimate treatment of obesity in humans, as available in scientific databases and published through July 2024. Lifestyle modifications (such as calorie restriction, intermittent fasting, physical exercise), including following a diet rich in flavonoids, antioxidants, specific fatty acids, specific amino acids and others, have shown a beneficial role in the induction of this process. The activation of autophagy through various nutritional interventions tends to elicit a consistent response, characterized by the induction of certain kinases (including AMPK, IKK, JNK1, TAK1, ULK1, and VPS34) or the suppression of others (like mTORC1), the deacetylation of proteins, and the alleviation of inhibitory interactions between BECN1 and members of the Bcl-2 family. Significant health/translational properties of many nutrients (nutraceuticals) can affect chronic disease risk through various mechanisms that include the activation or inhibition of autophagy. The role of nutritional intervention in the regulation of autophagy in obesity and its comorbidities is not yet clear, especially in obese individuals.

The post-oral sensing of bitter compounds by a family of bitter taste receptors (TAS2Rs) is suggested to regulate postprandial glycemia in humans. However, reports are inconsistent. This systematic review used meta-analysis to synthesise the impact of bitter compound interventions on the postprandial glycaemic response in humans.

Electronic databases (Medline, PubMed, and Web of Science) were systematically searched from inception to April 2024 to identify randomised controlled trials reporting the effect of interventions utilising post-oral bitter compounds vs. placebo on postprandial plasma glucose levels at t = 2 h (2 h-PPG), and area under the curve (AUC) of glucose, insulin, and c-peptide. The random-effect and subgroup analysis were performed to calculate pooled weighted mean differences (WMD), overall and by predefined criteria.

Forty-six studies (within 34 articles) were identified; 29 and 17 studies described chronic and acute interventions, respectively. The chronic interventions reduced 2 h-PPG (n = 21, WMD = -0.35 mmol/L, 95%CIs = -0.58, -0.11) but not AUC for glucose or insulin. Subgroup analysis showed the former was particularly evident in individuals with impaired glycemia, interventions longer than three months, or quinine family administration. The acute interventions did not improve the postprandial glycemia response, but subgroup analysis revealed a decrease in AUC-glucose after quinine family administration (n = 4 WMD = -90.40 (nmol × time/L), 95%CIs = -132.70, -48.10).

Chronic bitter compound interventions, particularly those from the quinine family, may have therapeutic potential in those with glycemia dysregulation. Acute intervention of the quinine family may also improve postprandial glucose. Given the very low quality of the evidence, further investigations with more rigorous methods are still required.

The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.

It may not always be possible for obese individuals to limit energy intake or to provide and/or maintain greater energy expenditure through exercise and physical activity. Therefore, the search for effective methods for obesity continues. Recently, the anti-obesity effect of stilbenes has attracted attention. In this review, aim was evaluating the effect of pterostilbene and resveratrol against obesity and the possible mechanisms in this effect. Dietary phytochemicals can induce body weight loss by increasing basal metabolic rate and thermogenesis and/or altering lipid metabolism. Stilbenes are products of the plant phenylpropanoid pathway. Very important mechanisms for the anti-obesity impact belonging to resveratrol as well as pterostilbene include thermogenic activation in brown adipose tissue alongside the browning of white adipose tissue. Considering nutrition and dietary habits, which have an important place in lifestyle changes for both the prevention and the treatment of obesity, pterostilbene and resveratrol, which are polyphenols and stilbenes, are seen as promising. However, optimal dose, duration, mechanism, long-term safety, side effects, combination, elucidation of genomic interactions, and lifestyle modifications should be considered.

Aging is generally accompanied by a progressive loss of metabolic homeostasis. Targeting metabolic processes is an attractive strategy for healthy-aging. Numerous natural compounds have demonstrated strong anti-aging effects. This review summarizes recent findings on metabolic pathways involved in aging and explores the anti-aging effects of natural compounds by modulating these pathways. The potential anti-aging effects of natural extracts rich in biologically active compounds are also discussed. Regulating the metabolism of carbohydrates, proteins, lipids, and nicotinamide adenine dinucleotide is an important strategy for delaying aging. Furthermore, phenolic compounds, terpenoids, alkaloids, and nucleotide compounds have shown particularly promising effects on aging, especially with respect to metabolism regulation. Moreover, metabolomics is a valuable tool for uncovering potential targets against aging. Future research should focus on identifying novel natural compounds that regulate human metabolism and should delve deeper into the mechanisms of metabolic regulation using metabolomics methods, aiming to delay aging and extend lifespan.

Introduction: fat tissue is an organ with endocrine function, where the hormone leptin (LEP) is identified. This peptide regulates appetite, the immune system, vascular functions and insulin sensitivity. Zinc (Zn) and resveratrol (RES) have potential effects on adipose tissue. Objective: to know if the combined administration of Zn and RES has any effect on blood leptin quantification in obese people. Methods: longitudinal experimental study, controlled clinical trial design, randomized, double blind. Randomized formation of four groups: T1 (Zn 50 mg), T2 (control), T3 (RES 500 mg), T4 (Zn 50 mg and RES 500 mg) with a supplementation period of 60 days. Blood samples were taken and glucose (GLU), leptin (LEP) and lipids (HDL, LDL, TGL) were quantified before and after exposure to the study elements. Results: age 34 (± 7) years. In T-tests, significance in GLU (p = 0.04) and LEP (p = 0.055). By exposure groups: GLU at T1 (p = 0.03) and T2 (p = 0.031); at LEP at T4 (p = 0.024). Lipids by groups: HDL at T3 (p = 0.039) and T4 (p = 0.014). ANOVA, HDL (p = 0.06). Pearson, HDL (p = 0.07) and LDL (p = 0.09). Conclusion: zinc and resveratrol showed promise as agents in modulating leptin and glucose signaling, confirming that they work in a proportional manner and provide benefits for cardiac health, but more exposure time is needed to see if they impact energy balance homeostasis.

Metabolism-related diseases, including diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease, are becoming increasingly prevalent, thereby posing significant threats to human health and longevity. Proteins, as the primary mediators of biological activities, undergo various posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and SUMOylation, among others, which substantially diversify their functions. These modifications are crucial in the physiological and pathological processes associated with metabolic disorders. Despite advancements in the field, there remains a deficiency in contemporary summaries addressing how these modifications influence processes of metabolic disease. This review aims to systematically elucidate the mechanisms through which PTM of proteins impact the progression of metabolic diseases, including diabetes, obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Additionally, the limitations of the current body of research are critically assessed. Leveraging PTMs of proteins provides novel insights and therapeutic targets for the prevention and treatment of metabolic disorders. Numerous drugs designed to target these modifications are currently in preclinical or clinical trials. This review also provides a comprehensive summary. By elucidating the intricate interplay between PTMs and metabolic pathways, this study advances understanding of the molecular mechanisms underlying metabolic dysfunction, thereby facilitating the development of more precise and effective disease management strategies.

Metabolic flexibility (MetF), defined as the ability to switch between fat and glucose oxidation, is increasingly recognised as a critical marker for assessing responses to dietary interventions. Previously, we showed that the consumption of multifibre bread improved insulin sensitivity and reduced low-density lipoprotein cholesterol (LDLc) levels in overweight and obese individuals. As a secondary objective, we aimed to explore whether our intervention could also improve MetF.

In this study, 39 subjects at cardiometabolic risk participated in a double-blind, randomised, crossover trial lasting 8 weeks, repeated twice. During each phase, participants consumed either 150 g of standard bread daily or bread enriched with a mixture of seven dietary fibres. MetF response was assessed using a mixed-meal tolerance test (MMTT), analysing changes in respiratory quotient (∆RQ) measured using indirect calorimetry.

Although there were no significant differences in ∆RQ changes induced by dietary fibre between the two diets, these changes were positively correlated with postprandial triglyceride excursion (∆TG) at baseline. Subgroup analysis of baseline fasting and postprandial plasma metabolites was conducted to characterise MetF responders. These responders exhibited higher baseline fasting LDLc levels and greater post-MMTT ∆TG.

In conclusion, although dietary fibres did not directly impact MetF in this study, our findings highlight potential determinants of MetF response, warranting further investigation in dedicated future interventions.

Src homology 2 B adaptor protein 1 (SH2B1) gene and variants have been found to be associated with common obesity. We aimed to investigate the association between the common missense variant SH2B1 rs7498665 and common obesity risk as well as interactions with lifestyle variables in an Israeli population.

An adult cohort (n=3,070; ≥18 years) with the SH2B1 rs7498665 variant and lifestyle, behavior (online questionnaire), and blood glucose data was analyzed. Associations between this variant, obesity risk (body mass index [BMI] ≥25 and ≥30 kg/m2), and interactions with behavioral and lifestyle factors (stress levels, eating habits score [EHS], physical activity [PA], and wine consumption) were investigated. Association and gene-environment interactions were analyzed using binary logistic regressions with interaction.

SH2B1 rs7498665 carriers were significantly (P<0.05) more likely to be overweight (BMI ≥25 kg/m2) or obese (BMI ≥30 kg/m2) in recessive (odds ratio [OR], 1.90 and 1.36, respectively), additive (OR, 1.24 and 1.14, respectively), and codominant (OR, 2.00 and 1.41, respectively) genetic models. SH2B1 rs7498665 interacted with lifestyle and behavioral factors as well as glucose levels. PA and moderate wine consumption (1 to 3 drinks/week) reduced obesity risk (OR, 0.35 and 0.71, respectively). Conversely, carriers of two risk alleles who reported high stress levels, had ≥median EHS, and who had a fasting glucose level ≥90 mg/dL had a significantly increased obesity risk (OR, 3.63 and 5.82, respectively).

Carrying SH2B1 rs7498665 significantly elevates the risk of obesity. Actionable lifestyle and behavioral factors significantly modulate the rs7498665 genetic predisposition to obesity; PA and moderate wine consumption attenuate the risk, while high stress, EHS, and fasting glucose level increase the obesity risk.

Background: Aging is a natural biological process influenced by multiple factors and is a significant contributor to various chronic diseases. Slowing down the aging process and extending health span have been pursuits of the scientific field. Methods: Examination of the effects of dietary polyphenols on hallmarks of aging such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Results: Polyphenols, abundant in nature, exhibit numerous biological activities, including antioxidant effects, free radical scavenging, neuroprotection, and anti-aging properties. These compounds are generally safe and effective in potentially slowing aging and preventing age-related disorders. Conclusions: The review encourages the development of novel therapeutic strategies using dietary polyphenols to create holistic anti-aging therapies and nutritional supplements.

In this editorial, we comment on the article published in the recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function. Ferroptosis and pyroptosis, cell death forms that can be initiated or blocked concurrently, can play significant roles in developing inflammation and various malignancies. However, their roles in ALF remain unclear. The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF, and revealed that the silent information regulator sirtuin 1 (SIRT1) inhibits both pathways through p53, dramatically reducing inflammation and protecting hepatocytes. This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF. Thus, we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms. Additionally, we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways, as well as examples of SIRT1 activators being used as disease treatment strategies, providing new insights into the therapy of ALF.

PURPOSE OF REVIEW: The global obesity epidemic has become a major public health concern, necessitating comprehensive research into its adverse effects on various tissues within the human body. Among these tissues, skeletal muscle has gained attention due to its susceptibility to obesity-related alterations. Mitochondria are primary source of energy production in the skeletal muscle. Healthy skeletal muscle maintains constant mitochondrial content through continuous cycle of synthesis and degradation. However, obesity has been shown to disrupt this intricate balance. This review summarizes recent findings on the impact of obesity on skeletal muscle mitochondria structure and function. In addition, we summarize the molecular mechanism of mitochondrial quality control systems and how obesity impacts these systems. RECENT FINDINGS: Recent findings show various interventions aimed at mitigating mitochondrial dysfunction in obese model, encompassing strategies including caloric restriction and various dietary compounds. Obesity has deleterious effect on skeletal muscle mitochondria by disrupting mitochondrial biogenesis and dynamics. Caloric restriction, omega-3 fatty acids, resveratrol, and other dietary compounds enhance mitochondrial function and present promising therapeutic opportunities.

Nicotinamide adenine dinucleotide (NAD+) is a central and pleiotropic metabolite involved in cellular energy metabolism, cell signaling, DNA repair, and protein modifications. Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Metabolic stress and aging directly affect the cardiovascular system. Compelling data suggest that NAD + levels decrease with age, obesity, and hypertension, which are all notable risk factors for CVD. In addition, the therapeutic elevation of NAD + levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular disorders. In preclinical models, NAD + boosting can also expand the health span, prevent metabolic syndrome, and decrease blood pressure. Moreover, NAD + storage by genetic, pharmacological, or natural dietary NAD + -increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models, and human health. Here, we review and discuss NAD + -related mechanisms pivotal for vascular health and summarize recent experimental evidence in NAD + research directly related to vascular disease, including atherosclerosis, and coronary artery disease. Finally, we comparatively assess distinct NAD + precursors for their clinical efficacy and the efficiency of NAD + elevation in the treatment of major CVD. These findings may provide ideas for new therapeutic strategies to prevent and treat CVD in the clinic.

The acute manifestations of coronavirus disease 2019 (COVID-19) exhibit the hallmarks of sepsis-associated complications that reflect multiple organ failure. The inflammatory cytokine storm accompanied by an imbalance in the pro-inflammatory and anti-inflammatory host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to severe and critical septic shock. The sepsis signature in severely afflicted COVID-19 patients includes cellular reprogramming and organ dysfunction that leads to high mortality rates, emphasizing the importance of improved clinical care and advanced therapeutic interventions for sepsis associated with COVID-19. Phytochemicals of functional foods and nutraceutical importance have an incredible impact on the healthcare system, which includes the prevention and/or treatment of chronic diseases. Hence, in the present review, we aim to explore the pathogenesis of sepsis associated with COVID-19 that disrupts the physiological homeostasis of the body, resulting in severe organ damage. Furthermore, we have summarized the diverse pharmacological properties of some potent phytochemicals, which can be used as functional foods as well as nutraceuticals against sepsis-associated complications of SARS-CoV-2 infection. The phytochemicals explored in this article include quercetin, curcumin, luteolin, apigenin, resveratrol, and naringenin, which are the major phytoconstituents of our daily food intake. We have compiled the findings from various studies, including clinical trials in humans, to explore more into the therapeutic potential of each phytochemical against sepsis and COVID-19, which highlights their possible importance in sepsis-associated COVID-19 pathogenesis. We conclude that our review will open a new research avenue for exploring phytochemical-derived therapeutic agents for preventing or treating the life-threatening complications of sepsis associated with COVID-19.