Analysis of differential metabolites and metabolic pathways in adipose tissue of tree shrews (Tupaia belangeri) under gradient cooling acclimation.

In order to investigate the influence of gradient cooling acclimation on body mass regulation in tree shrews (Tupaia belangeri), white adipose tissue (WAT) and brown adipose tissue (BAT) in T. belangeri between the control group and gradient cooling acclimation group on day 56 were collected, body mass, food intake, thermogenic capacity, differential metabolites, and related metabolic pathways in WAT and BAT were measured, the changes of differential metabolites were analyzed by non-targeted metabolomics method based on liquid chromatography-mass spectrometry. The results shown that gradient cooling acclimation significantly increased body mass, food intake, resting metabolic rate (RMR), non-shivering thermogenesis (NST), and masses of WAT and BAT. 23 significant differential metabolites in WAT between the gradient cooling acclimation group and the control group, of which the relative contents of 13 differential metabolites were up-regulated and 10 differential metabolites were down-regulated. 27 significant differential metabolites in BAT, of which 18 differential metabolites decreased and 9 differential metabolites increased. 15 differential metabolic pathways in WAT, 8 differential metabolic pathways in BAT, and 4 differential metabolic pathways involved in both WAT and BAT, including Purine metabolism, Pyrimidine metabolism, Glycerol phosphate metabolism, Arginine and proline metabolism, respectively. All of the above results suggested that T. belangeri could use different metabolites of adipose tissue to withstand low temperature environments and enhance their survival.

Evidence for the 'rate-of-living' hypothesis between mammals and lizards, but not in birds, with field metabolic rate.

Longevity, an important life-history trait, is determined by extrinsic and/or intrinsic causing mortality. Here, we used body mass (BM), field metabolic rate (FMR), longevity, and female maturity data reported from 300 amniote species to test whether 1) longevity was related to BM, FMR and female maturity, and 2) FMR, female maturity, or both, had a direct effect on longevity and whether an indirect effect of FMR on female maturity improved model fit. The results showed that BM was positively correlated with longevity and FMR, but negatively correlated with mass-specific FMR (mFMR) in amniotes. Phylogenetic confirmatory path analysis showed that, in the best model, longevity had a direct negative correlation with mFMR in lizards, and an indirect negative correlation with mFMR through female maturity in mammals. However, longevity had a direct positive correlation with mFMR in birds. Furthermore, longevity was positively correlated with female maturity in endotherms (birds and mammals) but weakly correlated with female maturity in ectotherms (lizards). Thus, our results are consistent with the life-history theory and the "rate-of-living" hypothesis in lizards and mammals but not support them in birds.

Metabolomics on serum levels and liver of male Tupaia belangeri from 12 locations in China by GC-MS.

OBJECTIVES: To investigate adaptive strategies of Tupaia belangeri to environmental factors in different populations, 12 locations were selected, including higher and lower altitude areas. RESULTS: Total of 96 and 90 metabolites were annotated in serum and liver respectively, which were mainly concentrated in primary metabolites. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed that the locations were divided into two groups in serum metabolites, but each group had a few samples overlap. The samples of each group overlap to some degree in the liver metabolites. The tricarboxylic acid (TCA) cycle occupies a central position in metabolism. The concentrations of TCA intermediates, lipid metabolites and amino acid metabolites were higher in higher altitude areas, and the concentrations of carbohydrate and glycolysis intermediates were higher in lower altitude areas. CONCLUSIONS: Different areas adapted to the changes of environmental and altitude by regulating the concentration of metabolites in serum and liver, and revealed the adaptive mechanism of T. belangeri in different living environments.

Methylation of the leptin gene promoter is associated with a negative correlation between leptin concentration and body fat in Tupaia belangeri.

AIMS: Leptin is a signaling protein secreted by white adipose tissue encoded by the obesity gene, and its main function is to regulate the food intake and energy metabolism in mammals. Previous studies had found that animal leptin concentration was positively correlated with its body fat, but the leptin concentration of Tupaia belangeri was negatively correlated with its body fat mass. The present study attempted to investigate the mechanisms of leptin concentration negatively correlated with its body fat mass in T. belangeri. MATERIAL AND METHODS: We measured the leptin concentration of the two groups of animals by enzyme linked immunosorbent assay (ELISA) and quantified the leptin mRNA expression by qPCR. Then, the histological, transcriptomic, and bisulfite sequencing of the two groups of animals were studied. Moreover, to investigate the energy metabolism under the negative correlation, we also analyzed the metabolomics and metabolic rate in T. belangeri. KEY FINDINGS: We revealed the negative correlation was mediated by leptin gene methylation of subcutaneous adipose tissue. Further, we also found that T. belangeri increased energy metabolism with leptin decreased. SIGNIFICANCE: We challenge the traditional view that leptin concentration was positively correlated with body fat mass, and further revealed its molecular mechanism and energy metabolism strategy. This special leptin secretion mechanism and energy metabolism strategy enriched our understanding of energy metabolism of animals, which provided an opportunity for the clinical transformation of metabolic diseases.

Emerging therapies: Potential roles of SGLT2 inhibitors in the management of pulmonary hypertension.

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and may be associated with a variety of cardiovascular and respiratory diseases. Pulmonary hypertension due to left heart disease (PH-LHD) currently lacks targeted therapies, while Pulmonary arterial hypertension (PAH), despite approved treatments, carries considerable residual risk. Metabolic dysfunction has been linked to the pathogenesis and prognosis of PH through various studies, with emerging metabolic agents offering a potential avenue for improving patient outcomes. Sodium-glucose cotransporter 2 inhibitor (SGLT-2i), a novel hypoglycemic agent, could ameliorate metabolic dysfunction and exert cardioprotective effects. Recent small-scale studies suggest SGLT-2i treatment may improve pulmonary artery pressure in patients with PH-LHD, and the PAH animal model shows that SGLT-2i can reduce pulmonary vascular remodeling and prevent progression in PAH, suggesting potential benefits for patients with PH-LHD and perhaps PAH. This review aims to succinctly review PH's pathophysiology, and the connection between metabolic dysfunction and PH, and investigate the prospective mechanisms of action of SGLT-2i in PH-LHD and PAH management.

Metagenomic comparison of intestinal microbiota between normal and liver fibrotic rhesus macaques (Macaca mulatta).

Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.

Effects of high-fiber food on gut microbiology and energy metabolism in Eothenomys miletus at different altitudes.

Intestinal microorganisms assist the host in digesting complex and difficultly decomposed foods; expand the host's dietary ecological niche. In order to investigate the effect of high-fiber food on intestinal microorganisms of Eothenomys miletus at different altitudes, exploring the regional differences of intestinal microorganisms and their roles in body mass regulation, we collected E. miletus from Dali (DL) and Xianggelila (XGLL), which were divided into control group, high-fiber group fed with high-fiber diet for 7 days, and refeeding group fed with standard diet for 14 days after high-fiber diet. Using 16S rRNA gene sequencing technology combined with physiological methods, we analyzed the gut microbial diversity, abundance, community structure and related physiological indicators of each group, and explored the effects of high-fiber foods and regions on the diversity, structure of gut microorganisms and physiological indicators. The results showed that high-fiber food affected the food intake and metabolic rate of E. miletus, which also showed regional differences. The intestinal microorganisms of E. miletus obtained energy through the enrichment of fiber degrading bacteria under the condition of high-fiber food, while producing short-chain fatty acids, which participated in processes such as energy metabolism or immune regulation. Moreover, it also affected the colonization of intestinal microorganisms. High-fiber food promoted the enrichment of probiotics in the intestinal microbiota of E. miletus, but pathogenic bacteria also appeared. Therefore, the changes in the composition and diversity of gut microbiota in E. miletus provided important guarantees for their adaptation to high fiber food environments in winter.

Population genomics provides insights into the evolution and adaptation of tree shrews (Tupaia belangeri) in China.

Physiological adaptation of tree shrews (Tupaia belangeri) to changing environmental temperature has been reported in detail. However, the T. belangeri origin (mainland or island), population history, and adaptation to historical climate change remain largely unknown or controversial. Here, for the first time, we sequenced the simplified genome of 134 T. belangeri individuals from 12 populations in China and further resequenced one individual from each population. Using population genomic approaches, we first observed considerable genetic variation in T. belangeri. Moreover, T. belangeri populations formed obvious genetic structure and reflected different demographic histories; they generally exhibited high genetic diversity, although the isolated populations had relatively low genetic diversity. The results presented in this study indicate that T. b. modesta and T. b. tonquinia were separated recently and with a similar population dynamics. Second, physical barriers rather than distance were the driving factors of divergence, and environmental heterogeneity may play an important role in genetic differentiation in T. belangeri. Moreover, our analyses highlight the role of historical global climates in the T. belangeri population dynamics and indicate that the decrease of the T. belangeri population size may be due to the low temperature. Finally, we identified the olfaction-associated adaptive genes between different altitude populations and found that olfactory-related genes of high-altitude populations were selectively eliminated. Our study provides demographic history knowledge of T. belangeri; their adaption history offers new insights into their evolution and adaptation, and provides valuable baseline information for conservation measures.

Effects of exogenous melatonin on body mass and thermogenesis in red-backed vole (Eothenomys miletus) between Kunming and Dali regions.

Melatonin (MEL) is an indole hormone synthesized and secreted by the pineal gland at night, which is involved in the regulation of body mass and thermogenesis in small mammals. To test the effects of exogenous MEL on body mass and thermogenic ability in two different red-backed vole (Eothenomys miletus) populations from two different regions (Kunming [KM] and Dali [DL]) with different annual variation in climatic variables, such as temperature, sunshine and rainfall. we traced the changes of energy balance in E. miletus from KM and DL, which were placed at 25 ± 1°C with photoperiod of 12 L:12 D, intraperitoneal injection of MEL was performed daily for 28 days. The results showed that body mass and food intake were significantly decreased, while resting metabolic rate (RMR) and nonshivering thermogenesis (NST) were significantly increased after MEL injection; Contents of total protein, mitochondrial protein, the activities of cytochrome C oxidase (COX) and α-glycerophosphate oxidase (α-PGO) in liver and brown adipose tissue (BAT) were enhanced; the activity of thyroxin 5'-deiodinase (T4 5'-DII) and uncoupling protein 1 (UCP1) in BAT were also increased. Serum leptin, triiodothyronine (T3 ) levels and T3 /T4 ratio were significantly increased, thyroxine (T4 ) levels was significantly decreased. Moreover, body mass and food intake in E. miletus from KM were higher than those from DL, but RMR and NST were lower than those from DL. Changes of body mass, food intake and thermogenic activity of KM were higher than those of DL when exposed to injection of MEL, indicating that E. miletus in KM were more sensitive to MEL. Furthermore, MEL was involved in the regulation of body mass and thermogenesis in E. miletus between KM and DL.

Butyrate and obesity: Current research status and future prospect.

Over the past few decades, increasing prevalence of obesity caused an enormous medical, social, and economic burden. As the sixth most important risk factor contributing to the overall burden of disease worldwide, obesity not only directly harms the human body, but also leads to many chronic diseases such as diabetes, cardiovascular diseases (CVD), nonalcoholic fatty liver disease (NAFLD), and mental illness. Weight loss is still one of the most effective strategies against obesity and related disorders. Recently, the link between intestinal microflora and metabolic health has been constantly established. Butyrate, a four-carbon short-chain fatty acid, is a major metabolite of the gut microbiota that has many beneficial effects on metabolic health. The anti-obesity activity of butyrate has been demonstrated, but its mechanisms of action have not been fully described. This review summarizes current knowledge of butyrate, including its production, absorption, distribution, metabolism, and the effect and mechanisms involved in weight loss and obesity-related diseases. The aim was to contribute to and advance our understanding of butyrate and its role in obesity. Further exploration of butyrate and its pathway may help to identify new anti-obesity.

Molecular genetics and quantitative traits divergence among populations of Eothenomys miletus from Hengduan Mountain region.

An important objective of evolutionary biology has always been to grasp the evolutionary and genetic processes that contribute to speciation. The present work provides the first detailed account of the genetic and physiological adaptation to changing environmental temperatures as well as the reasons causing intraspecific divergence in the Eothenomys miletus from the Hengduan Mountain (HM) region, one of the biodiversity hotspots. One hundred sixty-one E. miletus individuals from five populations in the HM region had their reduced-representation genome sequenced, and one additional individual from each community had their genomes resequenced. We then characterized the genetic diversity and population structure of each population and compared the phenotypic divergence in traits using neutral molecular markers. We detected significant phenotypic and genetic alterations in E. miletus from the HM region that were related to naturally occurring diverse habitats by combining morphometrics and genomic techniques. There was asymmetric gene flow among the E. miletus populations, indicating that five E. miletus populations exhibit an isolation-by-island model, and this was supported by the correlation between F ST and geographic distance. Finally, P ST estimated by phenotypic measures of most wild traits were higher than differentiation at neutral molecular markers, indicating directional natural selection favoring different phenotypes in different populations must have been involved to achieve this much differentiation. Our findings give information on the demographic history of E. miletus, new insights into their evolution and adaptability, and literature for studies of a similar nature on other wild small mammals from the HM region.

Clinical features and risk factors analysis for poor outcomes of severe community-acquired pneumonia in children: a nomogram prediction model.

Background: Pneumonia remains the leading cause of death among children aged 1-59 months. The early prediction of poor outcomes (PO) is of critical concern. This study aimed to explore the risk factors relating to PO in severe community-acquired pneumonia (SCAP) and build a PO-predictive nomogram model for children with SCAP. Methods: We retrospectively identified 300 Chinese pediatric patients diagnosed with SCAP who were hospitalized in the Affiliated Hospital of Southwest Medical University from August 1, 2018, to October 31, 2021. Children were divided into the PO and the non-PO groups. The occurrence of PO was designated as the dependent variable. Univariate and multivariate logistic regression analyses were used to identify the risk factors of PO. A nomogram model was constructed from the multivariate logistic regression analysis and internally validated for model discrimination and calibration. The performance of the nomogram was estimated using the concordance index (C-index). Results: According to the efficacy evaluation criteria, 56 of 300 children demonstrated PO. The multivariate logistic regression analysis resulted in the following independent risk factors for PO: co-morbidity (OR: 8.032, 95% CI: 3.556-18.140, P < 0.0001), requiring invasive mechanical ventilation (IMV) (OR: 7.081, 95% CI: 2.250-22.282, P = 0.001), and ALB < 35 g/L (OR: 3.203, 95% CI: 1.151-8.912, P = 0.026). Results of the internal validation confirmed that the model provided good discrimination (concordance index [C-index], 0.876 [95% CI: 0.828-0.925]). The calibration plots in the nomogram model were of high quality. Conclusion: The nomogram facilitated accurate prediction of PO in children diagnosed with SCAP and could be helpful for clinical decision-making.

Role of photoperiod on hormone concentrations and adaptive capacity in tree shrews, Tupaia belangeri.

Environmental factors, such as photoperiod and temperature, play an important role in the regulation of an animal's physiology and behavior. In the present study, we examined the effects of short photoperiod (SD, 8L:16D) on body mass as well as on several physiological, hormonal, and biochemical measures indicative of thermogenic capacity, to test our hypothesis that short photoperiod stimulates increases thermogenic capacity and energy intake in tree shrews. At the end, these tree shrews (SD) had a significant higher body mass, energy intake, cytochrome C oxidase (COX) activity and uncoupling protein-1 (UCP1) content, serum tri-iodothyronine (T(3)) and thyroxine (T(4)) compared to LD (16L:8D) tree shrews. However, there were no significant differences in serum leptin and melatonin between the two groups. Together, these data suggest tree shrews employ a strategy of maximizing body growth and increasing energy intake in response to cues associated with short photoperiod.

Energy metabolism, thermogenesis and body mass regulation in tree shrew (Tupaia belangeri) during subsequent cold and warm acclimation.

Environmental cues play important roles in the regulation of an animal's physiology and behavior. The purpose of the present study was to test the hypothesis that ambient temperature is a cue to induce adjustments in body mass, energy intake and thermogenic capacity, associated with changes in serum leptin levels in tree shrews (Tupaia belangeri). We found that tree shrews increased basal metabolic rate (BMR), energy intake and subsequently showed a significant decrease in body mass after being returned to warm ambient temperature. Uncoupling protein 1 (UCP1) content in brown adipose tissue (BAT) increased during cold acclimation and reversed after rewarming. The trend of energy intake increased during cold acclimation and decreased after rewarming; the trend of energy intake during cold acclimation was contrary to the trend of energy intake during rewarming. Further, serum leptin levels were negatively correlated with body mass. Together, these data supported our hypothesis that ambient temperature was a cue to induce changes in body mass and metabolic capacity. Serum leptin, as a starvation signal in the cold and satiety signal in rewarming, was involved in the processes of thermogenesis and body mass regulation in tree shrews.

Comparative research of intestinal microbiota diversity and body mass regulation in Eothenomys miletus from different areas of Hengduan mountain regions.

In order to investigate the effects of different areas on intestinal bacterial diversity and body mass regulation in Eothenomys miletus from Hengduan mountain regions, and to explore the community structure and diversity of intestinal microflora and their role in body mass regulation. E. miletus was collected from five areas including Deqin (DQ), Xianggelila (XGLL), Lijiang (LJ), Jianchuan (JC), and Dali (DL), we used 16S rRNA sequencing technology combined with physiological and morphological methods to study the intestinal microbiota diversity, abundance and community structure of the intestinal bacteria in winter, and to explore the influence of geographical factors, physiological indicators including food intake, resting metabolic rate (RMR), non-shivering thermogenesis (NST), neuropeptide Y (NPY), Agouti-Related Protein (AgRP), proopiomelanocortin (POMC), cocaine and amphetamine regulated transcription peptide (CART), and morphological indicators including body mass, body length and other nine indicators on the intestinal microflora diversity in E. miletus. The results showed that there were significant differences in metabolic indexes such as RMR, NST, NPY, AgRP, and morphological indexes such as body length, tail length and ear length among the five regions. Bacterial community in intestinal tract of E. miletus mainly includes three phyla, of which Firmicutes is the dominant phyla, followed by Bacteroidetes and Tenericutes. At the genus level, the dominant bacterial genera were S24-7(UG), Clostridiales (UG), and Lachnospiraceae (UG), etc. α diversity of intestinal microorganisms in DL and JC were significantly different from that in the other three regions. Genera of intestinal microorganisms in DL and JC were also the most. Moreover, Bacteroides, Ruminococcus, and Treponema could affect energy metabolism in E. miletus, which were closely related to the environment in which they lived. All of these results indicated that different areas in Hengduan Mountain had certain effects on the structure of intestinal microbial community in E. miletus, which were responded positively to changes in food abundance and other environmental factors. Furthermore, Firmicutes and Bacteroidetes play an important role in the body mass regulation in E. miletus.

Differences of energy adaptation strategies in Tupaia belangeri between Pianma and Tengchong region by metabolomics of liver: Role of warmer temperature.

Global warming is becoming the future climate trend and will have a significant impact on small mammals, and they will also adapt at the physiological levels in response to climate change, among which the adaptation of energetics is the key to their survival. In order to investigate the physiological adaptation strategies in Tupaia belangeri affected by the climate change and to predict their possible fate under future global warming, we designed a metabonomic study in T. belangeri between two different places, including Pianma (PM, annual average temperature 15.01°C) and Tengchong (TC, annual average temperature 20.32°C), to analyze the differences of liver metabolite. Moreover, the changes of resting metabolic rate, body temperature, uncoupling protein 1content (UCP1) and other energy indicators in T. belangeri between the two places were also measured. The results showed that T. belangeri in warm areas (TC) reduced the concentrations of energy metabolites in the liver, such as pyruvic acid, fructose 6-phosphate, citric acid, malic acid, fumaric acid etc., so their energy metabolism intensity was also reduced, indicating that important energy metabolism pathway of glycolysis and tricarboxylic acid cycle (TCA) pathway reduced in T. belangeri from warmer habitat. Furthermore, brown adipose tissue (BAT) mass, UCP1 content and RMR in TC also decreased significantly, but their body temperature increased. All of the results suggested that T. belangeri adapt to the impact of warm temperature by reducing energy expenditure and increasing body temperature. In conclusion, our research had broadened our understanding of the physiological adaptation strategies to cope with climate change, and also provided a preliminary insight into the fate of T. belangeri for the future global warming climate.

Roles of Ghrelin and Leptin in Body Mass Regulation under Food Restriction Based on the AMPK Pathway in the Red-Backed Vole, Eothenomys miletus, from Kunming and Dali Regions.

The phenotype plasticity of animals' physiological characteristics is an important survival strategy to cope with environmental changes, especially the change in climate factors. Small mammals that inhabit seasonally changing environments often face the stress of food shortage in winter. This study measured and compared the thermogenic characteristics and related physiological indicators in the adenosine-5'-monophosphate-activated protein kinase (AMPK) pathway in Eothenomys miletus between Kunming (KM, n = 18) and Dali (DL, n = 18) under food restriction and refeeding. The results showed that food restriction and the region have significant effects on body mass, the resting metabolic rate (RMR), hypothalamic neuropeptide gene expression, ghrelin levels in the stomach and serum, serum leptin level and the activity of AMPK, and malonyl CoA and carnitine palmitoyltransferase 1 (CPT-1) activity. Food restriction reduced the body mass, the gene expression of neuropeptide proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcription peptide (CART), and leptin level. However, the ghrelin concentration and AMPK activity increased. After refeeding, there was no difference in these physiological indexes between the food restriction and control groups. Moreover, the physiological indicators also showed regional differences, such as the body mass, POMC and CART gene expression, ghrelin concentration in the stomach and serum, and AMPK activity in DL changed more significantly. All these results showed that food restriction reduces energy metabolism in E. miletus. After refeeding, most of the relevant physiological indicators can return to the control level, indicating that E. miletus has strong phenotypic plasticity. Ghrelin, leptin, and the AMPK pathway play an important role in the energy metabolism of E. miletus under food restriction. Moreover, regional differences in physiological indicators under food restriction may be related to the different temperatures or food resources in different regions.

Roles of leptin on energy balance and thermoregulation in Eothenomys miletus.

Leptin is a hormone mainly synthesized and secreted by white adipose tissue (WAT), which regulates various physiological processes. To investigate the role of leptin in energy balance and thermoregulation in Eothenomys miletus, voles were randomly divided into leptin-injected and PBS-injected groups and placed at 25°C ± 1°C with a photoperiod of 12 L:12 D. They were housed under laboratory conditions for 28 days and compared in terms of body mass, food intake, water intake, core body temperature, interscapular skin temperature, resting metabolic rate (RMR), nonshivering thermogenesis (NST), liver and brown adipose tissue (BAT) thermogenic activity, and serum hormone levels. The results showed that leptin injection decreased body mass, body fat, food intake, and water intake. But it had no significant effect on carcass protein. Leptin injection increased core body temperature, interscapular skin temperature, resting metabolic rate, non-shivering thermogenesis, mitochondrial protein content and cytochrome C oxidase (COX) activity in liver and brown adipose tissue, uncoupling protein 1 (UCP1) content and thyroxin 5'-deiodinase (T45'-DII) activity in brown adipose tissue significantly. Serum leptin, triiodothyronine (T3), thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) concentrations were also increased significantly. Correlation analysis showed that serum leptin levels were positively correlated with core body temperature, body mass loss, uncoupling protein 1 content, thyroxin 5'-deiodinase activity, nonshivering thermogenesis, and negatively correlated with food intake; thyroxin 5'-deiodinase and triiodothyronine levels were positively correlated, suggesting that thyroxin 5'-deiodinase may play an important role in leptin-induced thermogenesis in brown adipose tissue. In conclusion, our study shows that exogenous leptin is involved in the regulation of energy metabolism and thermoregulation in E. miletus, and thyroid hormone may play an important role in the process of leptin regulating energy balance in E. miletus.

Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis via intro-adipose sympathetic innervation.

Emerging evidence suggests that butyrate, a short-chain fatty acid, may have beneficial effects on obesity and its associated metabolic comorbidities, but the related molecular mechanism is largely unknown. This study aims to investigate the role of butyrate in diet-induced obesity and metabolic disorders and the relevant regulatory mechanisms. Here, dietary supplementation with Sodium butyrate (NaB) was carried out in mice fed with a high-fat diet (HFD) or chow diet. At week 14, mice on HFD displayed an obese phenotype and down-regulated expression of thermogenic regulators including Ucp-1 and Pgc-1α in adipose tissue. Excitingly, NaB add-on treatment abolished these detrimental effects. Moreover, the obesity-induced insulin resistance, inflammation, fatty liver, and intestinal dysfunction were also attenuated by NaB administration. Mechanistically, NaB can promote fat thermogenesis via the increased local sympathetic innervation of adipose tissue, and blocking the ß3-adrenergic signaling pathway by 6-hydroxydopamine abolished NaB-induced thermogenesis. Our study reveals a potential pharmacological target for NaB to combat obesity and metabolic disorders.

Enoxacin ameliorates polycystic ovary syndrome by promoting the browning of white adipose tissue and restoring gut dysbiosis.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder syndrome characterized by polycystic ovary, ovulation disorder and hyperandrogenemia, and is often accompanied by metabolic disorders. Enoxacin has been reported to protect against diet-induced obesity and insulin resistance by promoting fat thermogenesis. However, the function of enoxacin in PCOS remains unknown. This study aimed to investigate the impact of the enoxacin on the regulation of PCOS mouse model induced by dehydroepiandrosterone (DHEA). Here, we found that reproductive endocrine disorder, glucose intolerance, and ovarian dysfunction in PCOS mice induced by DHEA were attenuated by enoxacin treatment. Mechanistically, we identified that enoxacin can promote white fat browning and improve metabolic disorders, thus ameliorating DHEA-induced reproductive dysfunction. Moreover, these beneficial effects might be associated with the restoration of gut dysbiosis. These findings provide a novel therapeutic target for enoxacin in the treatment of PCOS.