High-fat Diet-induced Obesity Research Articles

Preventing High Fat Diet-Induced Obesity and Related Hepatic Steatosis by Chlorin e6-Mediated Photodynamic Therapy.

Obesity and its associated hepatic steatosis have become a global concern, posing numerous health hazards. Photodynamic therapy (PDT) is a unique approach that promotes anti-obesity by releasing intracellular fat. Chlorin e6 (Ce6)-PDT was tested for its anti-obesity properties in male ovariectomized (OVX) beagle dogs, as well as male C57BL/6 and Balb/c mice. The 12 OVX beagles were randomly assigned to one of four groups: high-fat diet (HFD) only, Ce6 only, Ce6 + 10 min of light-emitting diode light (LED) treatment, and Ce6 + 15 min of light treatment. We assessed several parameters, such as body weight, adipose tissue morphology, serum biochemistry, and body fat content analysis by computed tomography (CT) scan in HFD-fed beagle dogs. At the end of the study period, dogs that were treated for 35 days with Ce6 and exposed to LED irradiation (660 nm) either for 10 min (Ce6 + 10 min of light) or for 15 min (Ce6 + 15 min of light) had decreased body weight, including visceral and subcutaneous fats, lower aspartate transaminase (AST)/alanine transaminase (ALT) ratios, and a reduction in the area of individual adipocytes with a concomitant increase in the number of adipocytes. Furthermore, C57BL/6 male mice following an HFD diet were effectively treated by Ce6-PDT treatment through a reduction in weight gain and fat accumulation. Meanwhile, Ce6-PDT attenuated hepatocyte steatosis by decreasing the epididymal adipose tissue and balloon degeneration in hepatocytes in HFD-fed Balb/c mice. Taken together, our results support the idea that Ce6-PDT is a promising therapeutic strategy for the recovery of obesity and obesity-related hepatic steatosis.

Diacylglycerol kinase delta overexpression improves glucose clearance and protects against the development of obesity

Background and aimDiacylglycerol kinase (DGK) isoforms catalyze an enzymatic reaction that removes diacylglycerol (DAG) and thereby terminates protein kinase C signaling by converting DAG to phosphatidic acid. DGKδ (type II isozyme) downregulation causes insulin resistance, metabolic inflexibility, and obesity. Here we determined whether DGKδ overexpression prevents these metabolic impairments. MethodsWe generated a transgenic mouse model overexpressing human DGKδ2 under the myosin light chain promoter (DGKδ TG). We performed deep metabolic phenotyping of DGKδ TG mice and wild-type littermates fed chow or high-fat diet (HFD). Mice were also provided free access to running wheels to examine the effects of DGKδ overexpression on exercise-induced metabolic outcomes. ResultsDGKδ TG mice were leaner than wild-type littermates, with improved glucose tolerance and increased skeletal muscle glycogen content. DGKδ TG mice were protected against HFD-induced glucose intolerance and obesity. DGKδ TG mice had reduced epididymal fat and enhanced lipolysis. Strikingly, DGKδ overexpression recapitulated the beneficial effects of exercise on metabolic outcomes. DGKδ overexpression and exercise had a synergistic effect on body weight reduction. Microarray analysis of skeletal muscle revealed common gene ontology signatures of exercise and DGKδ overexpression that were related to lipid storage, extracellular matrix, and glycerophospholipids biosynthesis pathways. ConclusionOverexpression of DGKδ induces adaptive changes in both skeletal muscle and adipose tissue, resulting in protection against high fat diet-induced obesity. DGKδ overexpression recapitulates exercise-induced adaptations on energy homeostasis and skeletal muscle gene expression profiles.

Oat avenanthramide B alleviates high-fat diet-induced obesity via regulating fatty acid metabolism involved in gut bacteria and fungi remodeling

Oat avenanthramide B alleviates high-fat diet-induced obesity via regulating fatty acid metabolism involved in gut bacteria and fungi remodeling

Apocynin exhibits an ameliorative effect on endothelial dysfunction/ atherosclerosis-related factors in high-fat diet-induced obesity in rats

Objective: The aim of this study was to reveal the effect of apocynin (APO) on the factors involved in obesity-related endothelial dysfunction (ED) and atherosclerosis (AS). Materials and Methods: Male Wistar albino rats were divided into control (CNT), high-fat diet (HFD) and HFD+APO groups. HFD and HFD+APO groups were fed HFD for sixteen weeks. APO (25 mg/kg) was administered to the HFD+APO group for the last four weeks. The effects of APO on: AS-related metabolic parameters (triglyceride, total cholesterol, high-density lipoprotein-cholesterol, insulin and leptin), oxidative stress (OS), [ malondialdehyde, glutathione, nicotinamide adenine dinucleotide phosphate (NADPH)- oxidase-2, oxidised-low-density lipoprotein (ox-LDL) and 8-hydroxy-2-deoxyguanosine], low-density lipoprotein and ox-LDL uptake potential (activin receptor-like kinase-1 and lectin-like oxidized low-density lipoprotein receptor-1, respectively), tissue inflammation (myeloperoxidase, monocyte-chemoattractant-protein-1, tumor necrosis factor-alpha), ED (endothelial-nitric oxide synthase, inducible-nitric oxide synthase, nitric oxide), programmed cell death (terminal deoxynucleotidyl-transferase-dUTP-nick-end labeling, cleaved-poly-ADP-ribose-polymerase, gasdermin-D N-terminal fragment, caspase-1), smooth muscle cell transformation (alpha-smooth muscle actin), histology and ultrastructure of thoracic aorta were evaluated. Results: In obesity, APO had an ameliorative effect on metabolic parameters, OS, inflammation, ED, programmed cell death and ox- LDL uptake potential, but not on foam cell formation and LDL uptake potential. Conclusion: Apocynin may improve ED and AS in obesity by suppressing OS-linked factors involved in the early stage of AS.

High fat diet-induced obesity and gestational DMBA exposure alter folliculogenesis and the proteome of the maternal ovary.

Obesity and ovotoxicant exposures impair female reproductive health with greater ovotoxicity reported in obese relative to lean females. The mother and developing fetus are vulnerable to both during gestation. 7,12-dimethylbenz[a]anthracene (DMBA) is released during carbon combustion including from cigarettes, coal, fossil fuels and forest fires. This study investigated the hypothesis that diet-induced obesity would increase sensitivity of the ovaries to DMBA-induced ovotoxicity and determined impacts of both obesity and DMBA exposure during gestation on the maternal ovary. Female C57BL/6J mice were fed a control (CT) or a High Sugar High Fat (HSHF; 45% kcal from fat; 20% kcal from sucrose) diet until ~30% weight gain was attained before mating with unexposed males. From gestation day 7, mice were exposed intraperitoneally to either vehicle control (corn oil) or DMBA (1mg/kg diluted in corn oil) for 7 d. Thus, there were four groups: lean control (LC); lean DMBA exposed (LD); obese control (OC); obese DMBA exposed (OD). Gestational obesity and DMBA exposure decreased (P < 0.05) ovarian and increased liver weights relative to LC dams, but there was no treatment impact (P > 0.05) on spleen weight or progesterone. Also, obesity exacerbated the DMBA reduction (P < 0.05) in the number of primordial, secondary follicles and corpora lutea. In lean mice, DMBA exposure altered abundance of 21 proteins; in obese dams, DMBA exposure affected 134 proteins while obesity alone altered 81 proteins in the maternal ovary. Thus, the maternal ovary is impacted by DMBA exposure and metabolic status influences the outcome.

Kidney Bean Protein Prevents High-Fat and High-Fructose Diet-Induced Obesity, Cognitive Impairment, and Disruption of Gut Microbiota Composition.

A long-term intake of a high-fat and high-fructose diet (HFFD), even a high-fat, high-fructose but low-protein diet (HFFD + LP), could cause obesity associated with cognitive impairments. In the present study, rats were subjected to a normal diet (ND), an HFFD diet, an HFFD + LP diet, and an HFFD with kidney bean protein (KP) diet for 8 weeks to evaluate the effect of KP on HFFD- or HFFD + LP-induced obesity and cognitive impairment. The results demonstrated that compared with the HFFD diet, KP administration significantly decreased the body weight by 7.7% and the serum Angiotensin-Converting Enzyme 2 (ACE-2) and Insulin-like Growth Factor 1 (IGF-1) levels by 14.4% and 46.8%, respectively (p < 0.05). In addition, KP suppressed HFFD-induced cognitive impairment, which was evidenced by 8.7% less time required to pass the water maze test. The 16s RNA analysis of the colonic contents showed that the relative abundance of Bifidobacterium, Butyricimonas, and Alloprevotella was increased by KP by 5.9, 44.2, and 79.2 times. Additionally, KP supplementation primarily affected the choline metabolic pathway in the liver, and the synthesis and functional pathway of neurotransmitters in the brain, thereby improving obesity and cognitive function in rats.

Amelioration of Insulin Resistance by Whey Protein in a High-Fat Diet-Induced Pediatric Obesity Male Mouse Model.

This study examined whey protein's impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared. The whey group showed significantly lower body weight than the casein group at 12 weeks old (p = 0.034). FBG was lower in the whey group compared to the high-fat diet group (p < 0.01) and casein group (p = 0.058); IRI and HOMA-IR were reduced in the whey group compared to the casein group (p = 0.02, p < 0.01, p < 0.01, respectively). The levels of peroxisome proliferator-activated receptor α and hormone-sensitive lipase were upregulated in the whey group compared to the casein group (p < 0.01, p = 0.03). Metabolomic analysis revealed that the levels of taurine and glycine, both known for their anti-inflammatory and antioxidant properties, were upregulated in the whey group in the liver tissue (p < 0.01, p < 0.01). The intake of whey protein was found to improve insulin resistance in a high-fat diet-induced pediatric obesity mouse model.

Reduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice

Whether intestinal Leucine-rich repeat containing G-protein-coupled receptor 4 (LGR4) impacts nutrition absorption and energy homeostasis remains unknown. Here, we report that deficiency of Lgr4 (Lgr4iKO) in intestinal epithelium decreased the proportion of enterocytes selective for long-chain fatty acid absorption, leading to reduction in lipid absorption and subsequent improvement in lipid and glucose metabolism. Single-cell RNA sequencing demonstrates the heterogeneity of absorptive enterocytes, with a decrease in enterocytes selective for long-chain fatty acid-absorption and an increase in enterocytes selective for carbohydrate absorption in Lgr4iKO mice. Activation of Notch signaling and concurrent inhibition of Wnt signaling are observed in the transgenes. Associated with these alterations is the substantial reduction in lipid absorption. Decrement in lipid absorption renders Lgr4iKO mice resistant to high fat diet-induced obesity relevant to wild type littermates. Our study thus suggests that targeting intestinal LGR4 is a potential strategy for the intervention of obesity and liver steatosis.

Knockdown of LAP2α inhibits adipogenesis of human adipose-derived stem cells and ameliorates high-fat diet-induced obesity.

Adipogenesis, a pivotal cellular process involving the differentiation of mesenchymal stem cells (MSCs) to mature adipocytes, plays a significant role in various physiological functions. Dysregulation of adipogenesis is implicated in conditions such as obesity. However, the complete molecular understanding of adipogenesis remains elusive. This study aimed to uncover the novel role of lamina-associated polypeptide 2 alpha (LAP2α) in human adipose-derived stem cells (hASCs) adipogenesis and its impact on high-fat diet (HFD)-induced obesity and associated metabolic disturbances. LAP2α expression was assessed during the adipogenic differentiation of hASCs using RT-qPCR and western blotting. The functional role of LAP2α in adipogenesis was explored both invitro and invivo through loss- and gain-of-function studies. Moreover, mice with HFD-induced obesity received lentivirus injection to assess the effect of LAP2α knockdown on fat accumulation. Molecular mechanisms underlying LAP2α in adipogenic differentiation were investigated using RT-qPCR, Western blotting, immunofluorescence staining, and Oil Red O staining. LAP2α expression was upregulated during hASCs adipogenic differentiation. LAP2α knockdown hindered adipogenesis, while LAP2α overexpression promoted adipogenic differentiation. Notably, LAP2α deficiency resisted HFD-induced obesity, improved glucose intolerance, mitigated insulin resistance, and prevented fatty liver development. Mechanistically, LAP2α knockdown attenuated signal transducer and activator of transcription 3 (STAT3) activation by reducing the protein level of phosphorylated STAT3. A STAT3 activator (Colivelin) counteracted the negative impact of LAP2α deficiency on hASCs adipogenic differentiation. Taken together, our current study established LAP2α as a crucial regulator of hASCs adipogenic differentiation, unveiling a new therapeutic target for obesity prevention.

Hypocholesterolemic potential of Bacillus amyloliquefaciens KAVK1 modulates lipid accumulation on 3T3-L1 adipose cells and high fat diet-induced obese rat model.

The significance of microorganisms occurring in foods is predominantly targeted due to their application for identifying a novel range of the bacterial spectrum. Diverse microbial species are capable of exhibiting potential pharmacological activities like antimicrobial and anticancer. Microbial strains capable of reducing obesity-related syndromes have also been reported. In the present study, the hypocholesterolemic efficacy of Bacillus amyloliquefaciens isolated from dairy products was scrutinised by in vitro (3T3-L1 adipose cells) and in vivo (high-fat diet-induced obese Wistar albino rats) methods. Potential cholesterol-lowering isolates were screened using a plate assay method and optimised by physical parameters. Molecular identification of the topmost five cholesterol-lowering isolates was acquired by amplification of the 16S rRNA gene region. Bacillus amyloliquefaciens strain KAVK1, followed by strains KAVK2, KAVK3, KAVK4, and KAVK5 were molecularly determined. Further, cholesterol-lowering strains degraded the spectral patterns determined by the side chain of a cholesterol molecule. The anti-lipase activity was demonstrated using the porcine pancreatic lipase inhibitory method and compared with the reference compound Atorvastatin. Lyophilised strain KAVK1 revealed maximum pancreatic lipase inhibition. Strain KAVK1 attenuated lipid accumulation in 3T3-L1 adipose cell line predicted by Oil Red O staining method. Significant reduction of body weight and change in lipid profile was recognised after the supplement of KAVK1 to obese rats. Histopathological changes in organs were predominantly marked. The result of this study implies that the cholesterol-lowering B. amyloliquefaciens KAVK1 strain was used to treat hypercholesterolemia.

Chronic administration of hydrolysed pine nut oil to mice improves insulin sensitivity and glucose tolerance and increases energy expenditure via a free fatty acid receptor 4-dependent mechanism.

A healthy diet is at the forefront of measures to prevent type 2 diabetes. Certain vegetable and fish oils, such as pine nut oil (PNO), have been demonstrated to ameliorate the adverse metabolic effects of a high-fat diet. The present study study investigates the involvement of the free fatty acid receptors 1 (FFAR1) and 4 (FFAR4) in the chronic activity of hydrolysed PNO (hPNO) on high-fat diet-induced obesity and insulin resistance. Male C57BL/6J wild-type, FFAR1 knockout (-/-) and FFAR4-/- mice were placed on 60% high-fat diet for 3 months. Mice were then dosed hPNO for 24 days, during which time body composition, energy intake and expenditure, glucose tolerance and fasting plasma insulin, leptin and adiponectin were measured. hPNO improved glucose tolerance and decreased plasma insulin in the wild-type and FFAR1-/- mice, but not the FFAR4-/- mice. hPNO also decreased high-fat diet-induced bodyweight gain and fat mass, whilst increasing energy expenditure and plasma adiponectin. None of these effects on energy balance were statistically significant in FFAR4-/- mice but it was not shown that they were significantly less than in wild-type mice. In conclusion, chronic hPNO supplementation reduces the metabolically detrimental effects of high-fat diet on obesity and insulin resistance in a manner that is dependent on the presence of FFAR4.

The impact of high-fat diet consumption and inulin fiber supplementation on anxiety-related behaviors and liver oxidative status in female Wistar rats

BackgroundObesity is a worldwide public health problem associated with cognitive and mental health problems in both humans and rats. Studies assessing the effect of fiber supplementation on behavioral deficits and oxidative stress caused by high-fat diet (HFD) consumption in female rats are still scarce. We hypothesized that HFD consumption would lead to anxiety-related behavior and hepatic oxidative stress and that inulin would protect against these changes. We analyzed the impact of HFD-induced obesity combined with fiber supplementation (inulin) on anxiety-related defensive behavior and hepatic oxidative stress. ResultsFemale rats were fed a high-fat diet (HFD; 45%) for nine weeks to induce obesity. The administration of inulin was found to decrease the adiposity index in both the control and obese groups. The consumption of a HFD combined with inulin supplementation resulted in a reduction in both CAT activity and carbonylated protein levels, leading to a shift in the hepatic redox balance. Interestingly, the behavioral data were conflicting. Specifically, animals that consumed a high-fat diet and received inulin showed signs of impaired learning and memory caused by obesity. The HFD did not impact anxiety-related behaviors in the female rats. However, inulin appears to have an anxiolytic effect, in the ETM, when associated with the HFD. On the other hand, inulin appears to have affected the locomotor activity in the HFD in both open field and light-dark box. ConclusionOur results show that consumption of a HFD induced obesity in female rats, similar to males. However, HFD consumption did not cause a consistent increase in anxiety-related behaviors in female Wistar rats. Treatment with inulin at the dosage used did not exert consistent changes on the behavior of the animals, but attenuated the abdominal WAT expansion and the hepatic redox imbalance elicited by high-fat diet-induced obesity.

Susceptibility to recombinant SARS-CoV-2 spike protein entry in the lungs of high-fat diet-induced obese mice.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Obesity is a major risk factor for the development of COVID-19. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for cell entry of SARS-CoV-2. The receptor-binding domain of the S1 subunit (S1-RBD protein) in the SARS-CoV-2 spike glycoprotein binds to ACE2 on host cells, through which the virus enters several organs, including the lungs. Considering these findings, recombinant ACE2 might be utilized as a decoy protein to attenuate SARS-CoV-2 infection. Here, we examined whether obesity increases ACE2 expression in the lungs and whether recombinant ACE2 administration diminishes the entry of S1-RBD protein into lung cells. We observed that high-fat diet-induced obesity promoted ACE2 expression in the lungs by increasing serum levels of LPS derived from the intestine. S1-RBD protein entered the lungs specifically through ACE2 expressed in host lungs and that the administration of recombinant ACE2 attenuated this entry. We conclude that obesity makes hosts susceptible to recombinant SARS-CoV-2 spike proteins due to elevated ACE2 expression in lungs, and this model of administering S1-RBD protein can be applied to new COVID-19 treatments.

Human milk oligosaccharide 2’-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice

ObjectiveTo decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We...

Clcn3 deficiency ameliorates high-fat diet-induced obesity and improves metabolism in mice.

Obesity is defined as excess body fat and is a current health epidemic associated with increased risk for type 2 diabetes and cardiovascular disease. The ClC-3 chloride channel/antiporter, encoded by the Clcn3, is associated with some diseases, like carcinoma, nervous system diseases, and metabolic diseases. To verify the relationship between the Clcn3 and weight including metabolic changes, searching for a new target for metabolic therapy of obesity, we designed the experiment. The mice were divided into 4 different groups: Clcn3+/+ mice + high-fat diet (HFD), Clcn3-/- mice + HFD, Clcn3+/+ mice + normal diet (ND), Clcn3-/- mice + ND, and fed for 16 weeks. After the glucose tolerance test and insulin tolerance test, peripheral blood and adipose tissues were collected. Moreover, we performed transcriptome sequencing for the epididymal white adipose tissue from Clcn3+/+ and Clcn3-/- mice with the high-fat diet. Western blotting verified the changes in protein levels of relevant metabolic genes. We found that the Clcn3-/- mice had lower body weight and visceral fat, refining glucose and lipid metabolism in HFD-induced mice, but had no effect in normal diet mice. RNA-seq and Western blotting indicated that Clcn3 deficiency may inhibit obesity through the AMPK-UCP1 axis. Modulation of Clcn3 may provide an appealing therapeutic target for obesity and associated metabolic syndrome.

The Long Non-Coding RNA Obesity-Related (Obr) Contributes To Lipid Metabolism Through Epigenetic Regulation.

Obesity is a multifactorial disease that is part of today's epidemic and also increases the risk of other metabolic diseases. Long noncoding RNAs (lncRNAs) provide one tier of regulatory mechanisms to maintain metabolic homeostasis. Although lncRNAs are a significant constituent of the mammalian genome, studies aimed at their metabolic significance, including obesity, are only beginning to be addressed. Here, a developmentally regulated lncRNA, termed as obesity related (Obr), whose expression in metabolically relevant tissues such as skeletal muscle, liver, and pancreas is altered in diet-induced obesity, is identified. The Clone 9 cell line and high-fat diet-induced obese Wistar rats are used as a model system to verify the function of Obr. By using stable expression and antisense oligonucleotide-mediated downregulation of the expression of Obr followed by different molecular biology experiments, its role in lipid metabolism is verified. It is shown that Obr associates with the cAMP response element-binding protein (Creb) and activates different transcription factors involved in lipid metabolism. Its association with the Creb histone acetyltransferase complex, which includes the cAMP response element-binding protein (CBP) and p300, positively regulates the transcription of genes involved in lipid metabolism. In addition, Obr is regulated by Pparγ in response to lipid accumulation.

The impact of eosinophilia on high fat diet-induced obesity and airway hyperresponsiveness

Hypothesis/Rationale: Eosinophils contribute to both adipose tissue metabolic homeostasis in obesity and airway hyperresponsiveness in asthma, but the role of eosinophils in obesity-related airway hyperresponsiveness is not understood. Considering that metabolic disorders increase the susceptibility to airway hyperresponsiveness in obese individuals, we investigated whether adipose eosinophils play a protective role in obesity-related airway hyperresponsiveness. Methods: Wild type (WT) and transgenic mice that overexpress interleukin 5 in peripheral T cells (+IL5T) were fed a high fat (61.6% fat) or normal chow (13.6% fat) diet for 19 weeks. Body weight, body fat, fasting glucose and insulin, and bronchoconstriction in response to inhaled serotonin were measured. The number of eosinophils were counted using flow cytometry in lung, adipose, and blood from transgenic WT and +IL5T mice with GFP-expressing eosinophils. Data: High fat diet significantly increased body weight and body fat in both WT and +IL5T mice, however +IL5T mice gained less weight and body fat than the WT mice. High fat diet increased fasting glucose, fasting insulin, and nerve-mediated airway responsiveness to inhaled serotonin in only the WT mice. On a normal chow diet, +IL5T mice had significantly more eosinophils in lung, blood, and adipose, and high fat diet further increased eosinophils in +IL5T adipose tissue. Acute administration of 1.29 U/kg (i.p.) insulin to a WT mouse on a normal chow diet significantly potentiated airway hyperresponsiveness to inhaled serotonin. Summary of results: Eosinophils in adipose tissue prevented high fat diet increases in circulating glucose and insulin, resulting in less body weight and body fat. This reduction in insulin by eosinophils in adipose tissue prevented obesity-related airway hyperresponsiveness. Conclusions: Insulin is a key modulator of obesity-related airway hyperresponsiveness. Eosinophils in adipose tissue play an important role in preventing obesity-related airway hyperresponsiveness by modulating insulin levels. Funding: NIH HL164474, NIH HL163087. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Reoxygenation Mitigates Intermittent Hypoxia-Induced Systemic Inflammation and Gut Microbiota Dysbiosis in High-Fat Diet-Induced Obese Rats.

Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its standard treatment. However, the effects of intermittent hypoxia/reoxygenation (IH/R) on weight regulation in obesity and its underlying mechanism remain unclear. Gut microbiota has gained attention for its strong association with various diseases. This study aims to explore the combined influence of IH and obesity on gut microbiota and to investigate the impact of reoxygenation on IH-induced alterations. Diet-induced obese (DIO) rats were created by 8-week high-fat diet (HFD) feeding and randomly assigned into three groups (n=15 per group): normoxia (NM), IH (6% O2, 30 cycles/h, 8 h/day, 4 weeks), or hypoxia/reoxygenation (HR, 2-week IH followed by 2-week reoxygenation) management. After modeling and exposure, body weight and biochemical indicators were measured, and fecal samples were collected for 16S rRNA sequencing. DIO rats in the IH group showed increased weight gain (p=0.0016) and elevated systemic inflammation, including IL-6 (p=0.0070) and leptin (p=0.0004). Moreover, IH rats exhibited greater microbial diversity (p<0.0167), and significant alterations in the microbial structure (p=0.014), notably the order Clostridiales, accompanied by an upregulation of bile acid metabolism predicted pathway (p=0.0043). Reoxygenation not only improved IH-exacerbated obesity, systemic inflammation, leptin resistance, and sympathetic activation, but also showed the potential to restore IH-induced microbial alterations. Elevated leptin levels were associated with Ruminococcaceae (p=0.0008) and Clostridiales (p=0.0019), while body weight was linked to Blautia producta (p=0.0377). Additionally, the abundance of Lactobacillus was negatively correlated with leptin levels (p=0.0006) and weight (p=0.0339). IH leads to gut dysbiosis and metabolic disorders, while reoxygenation therapy demonstrates a potentially protective effect by restoring gut homeostasis and mitigating inflammation. It highlights the potential benefits of CPAP in reducing metabolic risk among obese patients with OSA.

Piperine regulates the circadian rhythms of hepatic clock gene expressions and gut microbiota in high-fat diet-induced obese rats

The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes, and circadian desynchrony triggered by high-fat diet (HFD) is closely related to metabolic disorders. In this study, the modulatory effects of piperine (PIP) on lipid metabolism homeostasis, gut microbiota community and circadian rhythm of hepatic clock gene expressions in obese rats were investigated. The Sprague-Dawley (SD) rats were fed with normal diet (ND), HFD and HFD supplemented with PIP, respectively. After 9 weeks, rats were sacrificed with tissue and fecal samples collected for circadian analysis. Results showed that chronic PIP administration ameliorated the obesity-induced alterations in lipid metabolism and dysregulation of hepatic clock gene expressions in obese rats. The gut microbial communities studied through 16S rRNA sequencing showed that PIP ameliorated the imbalanced microbiota and recovered the circadian rhythm of Lactobacillaceae, Desulfovibrionaceae, Paraprevotellaceae, and Lachnospiraceae. The fecal metabolic profiles indicated that 3-dehydroshikimate, cytidine and lithocholyltaurine were altered, which were involved in the amino acid and fatty acid metabolism process. These findings could provide theoretical basis for PIP to work as functional food to alleviate the lipid metabolism disorder, circadian rhythm misalignment, and gut microbiota dysbiosis with wide applications in the food and pharmaceutic industries.

Anti-obesity and hypo-lipidemic activity of Eleusine indica against high fat diet-induced obesity in rats

In present study the pharmacological activity of Eleusine indica extract for Anti-obesity and Hypo-lipidemic effects in animal model. The phytochemical components of extract like terpenoids, saponin, alkoids and flavonoids, which already implicated for anti-hyperlipidemic activity. There was a comparative reduction in body weight of methanolic extract of Eleusine indica treated groups at “200”and ‘400 mg’/kg, atorvastatin “10 mg”/kg .when compared to the high fat diet administered rats. The results also suggested that methanolic extract of Eleusine indica at “200mg”/kg and 400 mg/kg are capable preventing the body weight gain this result was in accordance with the result reported from previous study where a dose depedent decrease in the body weight was observed. This study also proved remarkable increased in locomotor activity when compared with high fat administered rats. Whereas in obese rats there was reduction in locomotors activity. Present study also reported that methanolic extract of Eleusine indica significant [P&lt;0.001] decreased the level of LDL and Triglycerides also apart from reduction in weight, supplementation with MEEI was observed to attenuate significantly [P&lt;0.01] decreased the levels of total cholesterol and significantly increased [P&lt;0.01] the HDL level in rats feed with HFD.