Recent advances on cyanidin-3-O-glucoside in preventing obesity-related metabolic disorders: A comprehensive review.

Anthocyanins, found in various pigmented plants as secondary metabolites, represent a class of dietary polyphenols known for their bioactive properties, demonstrating health-promoting effects against several chronic diseases. Among these, cyanidin-3-O-glucoside (C3G) is one of the most prevalent types of anthocyanins. Upon consumption, C3G undergoes phases I and II metabolism by oral epithelial cells, absorption in the gastric epithelium, and gut transformation (phase II & microbial metabolism), with limited amounts reaching the bloodstream. Obesity, characterized by excessive body fat accumulation, is a global health concern associated with heightened risks of disability, illness, and mortality. This comprehensive review delves into the biodegradation and absorption dynamics of C3G within the gastrointestinal tract. It meticulously examines the latest research findings, drawn from in vitro and in vivo models, presenting evidence underlining C3G's bioactivity. Notably, C3G has demonstrated significant efficacy in combating obesity, by regulating lipid metabolism, specifically decreasing lipid synthesis, increasing fatty acid oxidation, and reducing lipid accumulation. Additionally, C3G enhances energy homeostasis by boosting energy expenditure, promoting the activity of brown adipose tissue, and stimulating mitochondrial biogenesis. Furthermore, C3G shows potential in managing various prevalent obesity-related conditions. These include cardiovascular diseases (CVD) and hypertension through the suppression of reactive oxygen species (ROS) production, enhancement of endogenous antioxidant enzyme levels, and inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway and by exercising its cardioprotective and vascular effects by decreasing pulmonary artery thickness and systolic pressure which enhances vascular relaxation and angiogenesis. Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are also managed by reducing gluconeogenesis via AMPK pathway activation, promoting autophagy, protecting pancreatic ß-cells from oxidative stress and enhancing glucose-stimulated insulin secretion. Additionally, C3G improves insulin sensitivity by upregulating GLUT-1 and GLUT-4 expression and regulating the PI3K/Akt pathway. C3G exhibits anti-inflammatory properties by inhibiting the NF-κB pathway, reducing pro-inflammatory cytokines, and shifting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. C3G demonstrates antioxidative effects by enhancing the expression of antioxidant enzymes, reducing ROS production, and activating the Nrf2/AMPK signaling pathway. Moreover, these mechanisms also contribute to attenuating inflammatory bowel disease and regulating gut microbiota by decreasing Firmicutes and increasing Bacteroidetes abundance, restoring colon length, and reducing levels of inflammatory cytokines. The therapeutic potential of C3G extends beyond metabolic disorders; it has also been found effective in managing specific cancer types and neurodegenerative disorders. The findings of this research can provide an important reference for future investigations that seek to improve human health through the use of naturally occurring bioactive compounds.

The adiponectin-derived peptide ALY688 protects against the development of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the severe form of non-alcoholic fatty liver disease which has a high potential to progress to cirrhosis and hepatocellular carcinoma, yet adequate effective therapies are lacking. Hypoadiponectinemia is causally involved in the pathogenesis of MASH. This study investigated the pharmacological effects of adiponectin replacement therapy with the adiponectin-derived peptide ALY688 (ALY688-SR) in a mouse model of MASH. Human induced pluripotent stem (iPS) cell-derived hepatocytes were used to test cytotoxicity and signaling of unmodified ALY688 in vitro. High-fat diet with low methionine and no added choline (CDAHF) was used to induce MASH and test the effects of ALY688-SR in vivo. Histological MASH activity score (NAS) and fibrosis score were determined to assess the effect of ALY688-SR. Transcriptional characterization of mice through RNA sequencing was performed to indicate potential molecular mechanisms involved. In cultured hepatocytes, ALY688 efficiently induced adiponectin-like signaling, including the AMP-activated protein kinase and p38 mitogen-activated protein kinase pathways, and did not elicit cytotoxicity. Administration of ALY688-SR in mice did not influence body weight but significantly ameliorated CDAHF-induced hepatic steatosis, inflammation, and fibrosis, therefore effectively preventing the development and progression of MASH. Mechanistically, ALY688-SR treatment markedly induced hepatic expression of genes involved in fatty acid oxidation, whereas it significantly suppressed the expression of pro-inflammatory and pro-fibrotic genes as demonstrated by transcriptomic analysis. ALY688-SR may represent an effective approach in MASH treatment. Its mode of action involves inhibition of hepatic steatosis, inflammation, and fibrosis, possibly via canonical adiponectin-mediated signaling.

Effects of high-quality protein supplementation on cardiovascular risk factors in individuals with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. METHODS: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. RESULTS: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. CONCLUSION: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders.

The role of tetrahydrocurcumin in disease prevention and treatment.

In recent decades, natural compounds derived from herbal medicine or dietary sources have played important roles in prevention and treatment of various diseases and have attracted more and more attention. Curcumin, extracted from the Curcumae Longae Rhizoma and widely used as food spice and coloring agent, has been proven to possess high pharmacological value. However, the pharmacological application of curcumin is limited due to its poor systemic bioavailability. As a major active metabolite of curcumin, tetrahydrocurcumin (THC) has higher bioavailability and stability than curcumin. Increasing evidence confirmed that THC had a wide range of biological activities and significant treatment effects on diseases. In this paper, we reviewed the research progress on the biological activities and therapeutic potential of THC on different diseases such as neurological disorders, metabolic syndromes, cancers, and inflammatory diseases. The extensive pharmacological effects of THC involve the modulation of various signaling transduction pathways including MAPK, JAK/STAT, NF-κB, Nrf2, PI3K/Akt/mTOR, AMPK, Wnt/ß-catenin. In addition, the pharmacokinetics, drug combination and toxicology of THC were discussed, thus providing scientific basis for the safe application of THC and the development of its dietary supplements and drugs.

[Guidelines for the prevention and treatment of metabolic dysfunction-associated (non-alcoholic) fatty liver disease (Version 2024)].

The Chinese Society of Hepatology of the Chinese Medical Association invited relevant experts to revise and update the Guideline of Prevention and Treatment of Nonalcoholic Fatty Liver Disease (2018Version) and renamed it as (Version 2024) Guideline for the Prevention and Treatment of Metabolic Dysfunction-associated (non-alcoholic) Fatty Liver Disease. Herein, the guiding recommendations on clinical issues such as screening and monitoring, diagnosis and evaluation, treatment and follow-up of metabolic dysfunction-associated fatty liver disease are put forward.

Usefulness of Opuntia spp. on the Management of Obesity and Its Metabolic Co-Morbidities.

The plants of the Opuntia genus mainly grow in arid and semi-arid climates. Although the highest variety of wild species is found in Mexico, Opuntia spp. is widely distributed throughout the world. Extracts of these cacti have been described as important sources of bioactive substances that can have beneficial properties for the prevention and treatment of certain metabolic disorders. The objective of this review is to summarise the presently available knowledge regarding Opuntia ficus-indica (nopal or prickly pear), and some other species (O. streptacantha and O. robusta) on obesity and several metabolic complications. Current data show that Opuntia ficus-indica products used in preclinical studies have a significant capacity to prevent, at least partially, obesity and certain derived co-morbidities. On this subject, the potential beneficial effects of Opuntia are related to a reduction in oxidative stress and inflammation markers. Nevertheless, clinical studies have evidenced that the effects are highly contingent upon the experimental design. Moreover, the bioactive compound composition of nopal extracts has not been reported. As a result, there is a lack of information to elucidate the mechanisms of action responsible for the observed effects. Accordingly, further studies are needed to demonstrate whether Opuntia products can represent an effective tool to prevent and/or manage body weight and some metabolic disorders.

Pemafibrate and other triglyceride-lowering therapies to reduce risk of cardiovascular and metabolic disease.

PURPOSE OF REVIEW: Although high triglycerides are consistently associated with elevated risk of cardiovascular disease (CVD), therapies that reduce triglyceride levels have inconsistently translated into reduced CVD risk. RECENT FINDINGS: To date, three clinical trials have tested triglyceride-lowering therapies in patients with hypertriglyceridemia (HTG) and elevated risk of incident/recurrent CVD. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), assignment to IPE, a highly purified eicosapentanoic acid (EPA), resulted in a 25% reduction in nonfatal myocardial infarction), nonfatal stroke, cardiovascular death, coronary revascularization and hospitalization for unstable angina. By contrast, the combination of EPA and docosahexanoic acid (DHA) carboxylic fatty acids used in the STRENGTH trial (Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia) failed to reduce CVD risk. Most recently, PROMINENT (Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes) also failed to demonstrate reduction in CVD events despite use of a potent triglyceride-lowering, fibric-acid derivative. However, improvement in HTG-associated metabolic complications (e.g. nonalcoholic fatty liver disease) was observed with pemafibrate as well as with another potent triglyceride-lowering therapy (i.e. pegozafermin). Moreover, trials are underway evaluating whether the most fatal metabolic complication of HTG, pancreatitis, may be reduced with highly potent triglyceride-lowering therapies (e.g. apolipoprotein C3 inhibitors). SUMMARY: Taken together, HTG is associated with increased risk of CVD and attendant adverse metabolic sequalae. To this end, a potentially promising and evidence-based landscape is emerging for treating a clinical phenotype that in the past has been insufficiently addressed.

Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18 adipocyte-specific knockout (Rab18 AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18 AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18 AKO mice had a moderate increase without ER stress stimulation. Rab18 AKO mice developed insulin resistance and systematic inflammation. Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Chrononutrition in the Prevention and Management of Metabolic Disorders: A Literature Review.

BACKGROUND: The concept of time-restricted eating (TRE) or time-restricted feeding (TRF) promotes daily periods of feeding and fasting to determine whole-body physiology. Chronic misalignment of circadian rhythms or chrono-disruption is related to an increased risk of diverse metabolic disorders. The progression of non-communicable diseases seems to be affected by the timing of meals. As a result, intermittent fasting is a promising approach for their management. The aim of the present literature review is to examine and scrutinize the TRE protocols in the fields of prevention and management of metabolic disorders. METHODS: This is a thorough literature review of the reported associations among circadian rhythm, metabolic disorders, diabetes mellitus, obesity, TRE, TRF, dietary habits, circadian disruption, cardiovascular diseases, atherosclerosis, and non-alcoholic fatty liver to find the already existing clinical studies from the last decade (2014-2024) in the most precise scientific online databases, using relevant specific keywords. Several inclusion and exclusion criteria were applied to scrutinize only longitudinal, cross-sectional, descriptive, and prospective clinical human studies. RESULTS: The currently available clinical findings remain scarce and suggest that chrononutrition behaviors such as TRE or TRF may promote several metabolic benefits, mainly in body weight control and fat loss. Improvements in glucose levels and lipid profiles are currently quite controversial since some clinical studies show little or no effect. As far as liver diseases are concerned, the efficacy of intermittent fasting seems to be stronger in the management of non-alcoholic fatty liver disease due to body weight decline and fat loss. CONCLUSIONS: Even if there has been a gradual increase in clinical studies in the last few years, providing promising perspectives, currently, there is no conclusive evidence for the role of chrononutrition in metabolic disorders. Future studies should be well-designed with longer duration and larger sample sizes. Moreover, it is important to examine the best timing of the eating window and its feasibility.

Preventing metabolic disease: Part I.

While the successes of modern medicine have significantly extended the human lifespan, the burden of chronic metabolic disease increasingly impacts the quality of life of almost two billion people worldwide. It is now imperative that we recognize metabolic disease as a pandemic and urgently prioritize preventive measures to halt its expansion.

Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation.

The escalating prevalence of metabolic and cardiometabolic disorders, often characterized by oxidative stress and chronic inflammation, poses significant health challenges globally. As the traditional therapeutic approaches may sometimes fall short in managing these health conditions, attention is growing toward nutraceuticals worldwide; with compounds being obtained from natural sources with potential therapeutic beneficial effects being shown to potentially support and, in some cases, replace pharmacological treatments, especially for individuals who do not qualify for conventional pharmacological treatments. This review delves into the burgeoning field of nutraceutical-based pharmacological modulation as a promising strategy for attenuating oxidative stress and inflammation in metabolic and cardiometabolic disorders. Drawing from an extensive body of research, the review showcases various nutraceutical agents, such as polyphenols, omega-3 fatty acids, and antioxidants, which exhibit antioxidative and anti-inflammatory properties. All these can be classified as novel nutraceutical-based drugs that are capable of regulating pathways to mitigate oxidative-stress- and inflammation-associated metabolic diseases. By exploring the mechanisms through which nutraceuticals interact with oxidative stress pathways and immune responses, this review highlights their potential to restore redox balance and temper chronic inflammation. Additionally, the challenges and prospects of nutraceutical-based interventions are discussed, encompassing bioavailability enhancement, personalized treatment approaches, and clinical translation. Through a comprehensive analysis of the latest scientific reports, this article underscores the potential of nutraceutical-based pharmacological treatment modulation as a novel avenue to fight oxidative stress and inflammation in the complex landscape of metabolic disorders, particularly accentuating their impact on cardiovascular health.

Maternal Phlorizin Intake Protects Offspring from Maternal Obesity-Induced Metabolic Disorders in Mice via Targeting Gut Microbiota to Activate the SCFA-GPR43 Pathway.

Maternal obesity increases the risk of obesity and metabolic disorders (MDs) in offspring, which can be mediated by the gut microbiota. Phlorizin (PHZ) can improve gut dysbiosis and positively affect host health; however, its transgenerational metabolic benefits remain largely unclear. This study aimed to investigate the potential of maternal PHZ intake in attenuating the adverse impacts of a maternal high-fat diet on obesity-related MDs in dams and offspring. The results showed that maternal PHZ reduced HFD-induced body weight gain and fat accumulation and improved glucose intolerance and abnormal lipid profiles in both dams and offspring. PHZ improved gut dysbiosis by promoting expansion of SCFA-producing bacteria, Akkermansia and Blautia, while inhibiting LPS-producing and pro-inflammatory bacteria, resulting in significantly increased fecal SCFAs, especially butyric acid, and reduced serum lipopolysaccharide levels and intestinal inflammation. PHZ also promoted intestinal GLP-1/2 secretion and intestinal development and enhanced gut barrier function by activating G protein-coupled receptor 43 (GPR43) in the offspring. Antibiotic-treated mice receiving FMT from PHZ-regulated offspring could attenuate MDs induced by receiving FMT from HFD offspring through the gut microbiota to activate the GPR43 pathway. It can be regarded as a promising functional food ingredient for preventing intergenerational transmission of MDs and breaking the obesity cycle.

Maternal methyl donor supplementation: A potential therapy for metabolic disorder in offspring.

The prevalences of diabetes mellitus and obesity are increasing yearly and has become a serious social burden. In addition to genetic factors, environmental factors in early life development are critical in influencing the prevalence of metabolic disorders in offspring. A growing body of evidence suggests the critical role of early methyl donor intervention in offspring health. Emerging studies have shown that methyl donors can influence offspring metabolism through epigenetic modifications and changing metabolism-related genes. In this review, we focus on the role of folic acid, betaine, vitamin B12, methionine, and choline in protecting against metabolic disorders in offspring. To address the current evidence on the potential role of maternal methyl donors, we summarize clinical studies as well as experimental animal models that support the impact of maternal methyl donors on offspring metabolism and discuss the mechanisms of action that may bring about these positive effects. Given the worldwide prevalence of metabolic disorders, these findings could be utilized in clinical practice, in which methyl donor supplementation in the early life years may reverse metabolic disorders in offspring and block the harmful intergenerational effect.

Gestational Diabetes and Long-Term Cardiometabolic Health.

This JAMA Insights discusses adverse long-term effects of gestational diabetes on the pregnant individual and the exposed fetus.

Intermittent Fasting and Physical Exercise for Preventing Metabolic Disorders through Interaction with Gut Microbiota: A Review.

Metabolic disorders entail both health risks and economic burdens to our society. A considerable part of the cause of metabolic disorders is mediated by the gut microbiota. The gut microbial structure and function are susceptible to dietary patterns and host physiological activities. A sedentary lifestyle accompanied by unhealthy eating habits propels the release of harmful metabolites, which impair the intestinal barrier, thereby triggering a constant change in the immune system and biochemical signals. Noteworthy, healthy dietary interventions, such as intermittent fasting, coupled with regular physical exercise can improve several metabolic and inflammatory parameters, resulting in stronger beneficial actions for metabolic health. In this review, the current progress on how gut microbiota may link to the mechanistic basis of common metabolic disorders was discussed. We also highlight the independent and synergistic effects of fasting and exercise interventions on metabolic health and provide perspectives for preventing metabolic disorders.

Physical Exercise and Diet: Regulation of Gut Microbiota to Prevent and Treat Metabolic Disorders to Maintain Health.

Each person's body is host to a large number and variety of gut microbiota, which has been described as the second genome and plays an important role in the body's metabolic process and is closely related to health. It is common knowledge that proper physical activity and the right diet structure can keep us healthy, and in recent years, researchers have found that this boost to health may be related to the gut microbiota. Past studies have reported that physical activity and diet can modulate the compositional structure of the gut microbiota and further influence the production of key metabolites of the gut microbiota, which can be an effective way to improve body metabolism and prevent and treat related metabolic diseases. In this review, we outline the role of physical activity and diet in regulating gut microbiota and the key role that gut microbiota plays in improving metabolic disorders. In addition, we highlight the regulation of gut microbiota through appropriate physical exercise and diet to improve body metabolism and prevent metabolic diseases, aiming to promote public health and provide a new approach to treating such diseases.

Ablation of miRNA-22 protects against obesity-induced adipocyte senescence and ameliorates metabolic disorders in middle-aged mice.

High-fat diet (HFD) promotes obesity-related metabolic complications by activating cellular senescence in white adipose tissue (WAT). Growing evidence supports the importance of microRNA-22 (miR-22) in metabolic disorders and cellular senescence. Recently, we showed that miR-22 deletion attenuates obesity-related metabolic abnormalities. However, whether miR-22 mediates HFD-induced cellular senescence of WAT remains unknown. Here, we uncovered that obese mice displayed increased pri-miR-22 levels and cellular senescence in WAT. However, miR-22 ablation protected mice against HFD-induced WAT senescence. In addition, in vitro studies showed that miR-22 deletion prevented preadipocyte senescence in response to Doxorubicin (Doxo). Loss-of-function studies in vitro and in vivo revealed that miR-22 increases H2ax mRNA and γH2ax levels in preadipocytes and WAT without inducing DNA damage. Intriguingly, miR-22 ablation prevented HFD-induced increase in γH2ax levels and DNA damage in WAT. Similarly, miR-22 deletion prevented Doxo-induced increase in γH2ax levels in preadipocytes. Adipose miR-22 levels were enhanced in middle-aged mice fed a HFD than those found in young mice. Furthermore, miR-22 deletion attenuated fat mass gain and glucose imbalance induced by HFD in middle-aged mice. Overall, our findings indicate that miR-22 is a key regulator of obesity-induced WAT senescence and metabolic disorders in middle-aged mice.

Targeting the gut to prevent and counteract metabolic disorders and pathologies during aging.

Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition and function of the microbiota it harbors. Continuous deteriorations are generally associated with the development of systemic dysregulations and ultimately pathologies that can worsen the initial health status of individuals. All these alterations observed at the gut level can then constitute a wide range of potential targets for development of nutritional strategies that can impact gut tissue or associated microbiota pattern. This can be key, in a preventive manner, to limit gut functionality decline, or in a curative way to help maintaining optimum nutrients bioavailability in a context on increased requirements, as frequently observed in pathological situations. The aim of this review is to give an overview on the alterations that can occur in the gut during aging and lead to the development of altered function in other tissues and organs, ultimately leading to the development of pathologies. Subsequently is discussed how nutritional strategies that target gut tissue and gut microbiota can help to avoid or delay the occurrence of aging-related pathologies.

The effect of Xuezhikang capsule on gene expression profile in brown adipose tissue of obese spontaneously hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is a critical threat to global health, and brown adipose tissue (BAT) is a potential target for the treatment of obesity and comorbidities. Xuezhikang Capsule (XZK), an extract of red yeast rice, has remarkable clinical efficacy and is widely used for the treatment of hyperlipidemia and coronary heart disease. However, its modulatory effect on BAT remains unknown. AIM OF THIS STUDY: The aim of this study was to investigate the protective mechanism of XZK in the obese spontaneously hypertensive rat (SHR) model by evaluating the regulatory effect of XZK on the BAT gene profile through transcriptome sequencing. MATERIALS AND METHODS: The SHRs were randomly divided into four groups: the standard chow diet (STD) group, the STD supplemented with 126 mg/kg of XZK group, the high-fat diet (HFD) group, and the HFD supplemented with 126 mg/kg of XZK group. All SHRs were fed for 18 weeks. The metabolic phenotypes, including body weight, fat mass, oral glucose tolerance test (OGTT), and serum glucose and lipid levels, was evaluated, and hematoxylin and eosin staining (H&E) staining was performed to evaluate the adipose tissue histopathological phenotype. Transcriptome sequencing was performed to determine the mechanism by which XZK improves the metabolic phenotype and the expression of key differential expression genes was verified by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: XZK inhibited HFD-induced weight gain and adipose tissue remodeling in SHRs and prevented hypertrophy of epididymal adipocytes and maintained the brown fat phenotype. XZK intervention also improved glucose and lipid metabolism in SHRs, as suggested by a reduction in serum triglyceride (TG), low-density cholesterol (LDL-C), and fasting blood glucose (FBG) levels as well as increasing in serum high-density cholesterol (HDL-C) levels. Transcriptome sequencing analysis confirmed the regulatory effect of XZK on the gene expression profile of BAT, and the expression patterns of 45 genes were reversed by the XZK intervention. Additionally, the results of the transcriptome analysis of 10 genes that are important for brown fat function were in line with the results of qRT-PCR. CONCLUSIONS: XZK protected SHRs from HFD-induced obesity, inhibited fat accumulation and improved glucolipid metabolism. Additionally, the protective effect of XZK on the overall metabolism of obese SHRs might partly be related to its regulatory effect on the BAT gene expression profile. These findings might provide novel therapeutic strategies for obesity-related metabolic diseases in traditional Chinese medicine (TCM).