High-fat Diet Group Research Articles

Abstract 4134475: Effects of E-cigarette Vaping on Endothelial Function in Diet-Induced Obese Mice

Introduction: Although electronic cigarettes (e-cigs) have been known to increase the risk of vascular complications, little is known about whether e-cig represents an independent risk factor for the development and worsening of obesity and its associated vascular diseases. We hypothesize that a high-fat diet (HFD) enhances e-cig-induced vascular complications. Methods: Male and female eight-week-old C57Bl/6J mice were fed normal chow (NC) or HFD for 15 weeks before being exposed to e-cigs (PG/VG only [PGVG] or PG/VG + 24 mg/ml nicotine [Nic]) or fresh air (FA) for 12 weeks (n=6-8). At the end of the experiments, glucose level and thoracic aortic responses to phenylephrine (PE), acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed via the glucose tolerance test (GTT) and wire myography, respectively. Total RNA from male aortas was extracted and RNA-seq was utilized to identify the transcriptomic changes in our diet-induced obesity mouse model subjected to e-cig vapors (n=4). Results: Compared to NC with FA, HFD alone caused glucose intolerance as shown by the GTT, which was improved only by exposure to nicotine-containing e-cigs (HFD+Nic). Similar improvement in glucose intolerance were found in the NC group with e-cigs (PGVG or Nic). In addition, both NC and HFD-fed male mice exhibited endothelial dysfunction characterized by a decrease in the ACh-dependent (endothelium) relaxation of PE-induced contractions. Importantly, nicotine-containing e-cig exposure (Nic) dramatically reduced the sensitivity of the aorta in the HFD group (HFD+Nic) to both ACh and SNP, while it only affected the sensitivity and maximum relaxation to ACh in the male NC group (NC+Nic). There were no significant differences in the vasoreactivity of female mice exposed to e-cig or HFD. Finally, RNA-seq results suggested that e-cig-treated male mice had altered expression of genes related to endothelial and smooth muscle function and metabolism, particularly fatty acid metabolism, which was also significant with the addition of HFD. Conclusion: Collectively, our results suggest that acute e-cig exposure results in significant vascular dysfunction in male mice, which is worsened in HFD mice. The identification of genes dysregulated in mice exposed to e-cigs provides novel insights into vascular biology and could have a significant impact on our understanding of vascular complications associated with e-cig usage and provide insights into its contributions to obesity and diabetes.

Lactobacillus plantarum KAD protects against high-fat diet-induced hepatic complications in Swiss albino mice: Role of inflammation and gut integrity

Hepatic complications are the major health issues associated with dietary intake of calorie saturated food e.g. high-fat diet (HFD). Recent studies have revealed the beneficial effects of probiotics in HFD fed mice with hepatic complications. Some probiotic Lactic acid bacteria (LAB) e.g. Lactobacillus plantarum have drawn our attention in managing hepatic complications. Here, we aim to elucidate the protective effects of L. plantarum KAD strain, isolated from ethnic fermented food ‘Kinema’ in HFD-fed mice as, a preventive approach. Eighteen Swiss albino mice were equally divided into 3 groups: Normal Diet (ND), negative control (HFD), and HFD-fed with oral L. plantarum KAD supplementation (LP). All the experimental groups were subjected to specific diet according to grouping for eight weeks. After completion of the regime, subjects were anesthetized and sacrificed. Organs, blood, and fecal samples were collected and stored appropriately. Physical indices, including body weight gain, organ co-efficients were calculated along with assessment of glycemic, lipidomic, hepatic, oxidative stress, inflammatory, and histological parameters. Gut microbiota analysis was performed using 16s V3-V4 fecal metagenomic profiling, and sequencing were done using Illumina Miseq system. Oral administration of L. plantarum KAD is found to significantly (p<0.05) restore metabolic health by normalizing glycemic, lipidomic, hepatic parameters, oxidative stress and inflammatory parameters. Moreover, LP group (7.08±0.52 mg/g) showed significantly (p<0.001) decreased hepatic triglyceride level compared to HFD group (20.07±1.32 mg/g). L. plantarum KAD improved the adipocytic, and colonic histomorphology with significantly better scoring pattern. LP group (1.83±0.41) showed a significantly (p<0.001) reduced hepatic score compared to negative control group (5.00±0.63), showing reduced hepatosteatosis, and immune infiltration. The strain modulated gut health by altering its microbial composition positively towards normalization. In conclusion, the results of the experiment suggest that prophylactic L. plantarum KAD administration has beneficial effects on the onset of HFD induced hepatic complications in mice. Further studies are needed, on this strain for its clinical use as dietary supplement.

Ligandrol Ameliorates High-Fat Diet- and Streptozotocin-Induced Type 2 Diabetes Mellitus and Prevents Pancreatic Islets Degeneration.

Androgen therapy has been shown to alleviate type 2 diabetes mellitus (T2DM) but is also associated with severe side effects such as prostate cancer. The present study aims to identify the best hit selective androgen receptor (AR) modulator by in silico studies and then investigates its antidiabetic effects in high-fat diet- and streptozotocin (STZ)-induced T2DM male rat model. Molecular docking and molecular dynamics (MD) studies were carried out using Maestro 13.1 and Desmond (2023-2024). Cytotoxicity and insulin secretion were measured in MIN6 cell lines. T2DM was induced using high-fat diet (HFD) for 4 weeks, followed by single STZ (40 mg/kg, intraperitoneally). OneTouch Ultra glucometer was used to measure fasting blood glucose. Gene expression was determined using reverse transcription polymerase chain reaction. Histopathology was carried out using hematoxylin and eosin stain. Through molecular docking, we identify ligandrol as a potential hit. Ligandrol showed a good binding affinity (-10.74 kcal/mol). MD showed that ligandrol is stable during the 100 ns simulation. Ligandrol increases insulin secretion in a dose-dependent manner in vitro in 2 h. Ligandrol (0.3 and 1 mg/kg, orally) significantly decreased the body weight and fasting blood glucose levels compared with the HFD and STZ group. Gene expression showed that ligandrol significantly increased the AR-targeted gene, neurogenic differentiation 1, compared with the HFD and STZ group. Histopathological staining studies showed that ligandrol prevents pancreatic islet degeneration compared with the HFD and STZ group. Our findings suggest that ligandrol's protective effect on pancreatic islets leading to its antidiabetic effect occurs through the activation of AR.

Euglena Attenuates High-Fat-Diet-Induced Obesity and Especially Glucose Intolerance

Background: Obesity, a global disease, can lead to different chronic diseases and a series of social health problems. Lifestyle changes, especially dietary changes, are the most effective way to treat obesity. Euglena, a novel food, has attracted much attention. Previous studies have shown that Euglena is an important modulator of the host immune response. In this study, the effects of Euglena as a nutritional intervention in high-fat-diet-induced obese C57BL/6J mice were investigated regarding adipose tissue accumulation and lipid and glucose metabolism by gavage at the dose of 100 mg/kg bodyweight for 9 weeks. This study is one of the few to investigate, in detail, the preventive effects of dietary Euglena on obesity. Methods: Five-week-old male C57BL/6J mice were fed with a high-fat diet (HFD) to induce obesity. An obesity model was created by feeding the high-fat diet for a period of 10 weeks. Obese mice were randomized into 2 groups with the same mean body weight, and no significant differences were observed between the groups: (1) the mice in the HEG group were maintained on a high-fat diet and daily gavaged with Euglena (100 mg/kg body weight) dissolved in saline (n = 7); and (2) the mice in the HFD group were maintained on a high-fat diet and daily gavaged with saline with the same volume (n = 7). The experiment finished after a nine-week period. Results: The results showed that Euglena could reduce the accumulation of white body fat, including subcutaneous fat and visceral fat, and mainly targeted subcutaneous fat. Euglena also reduced adipocyte particle size expansion, promoted lipolysis in adipose (adipose triglyceride lipase and hormone-sensitive triglyceride lipase) and liver tissue (reduced non-esterified fatty acid content), and improved obesity-induced ectopic fat deposition and glucose tolerance. Conclusions: Our findings suggest that Euglena, as a nutritional intervention in HFDs, efficiently reduces body weight and white adipose tissue deposition. The mechanism of Euglena is mainly though enhancing lipolysis. It is worth noting that Euglena β-glucan recovers the hyperglycemia and accumulation of ectopic fat within the liver induced by HFD. Our study is one of the few studies to report in detail the preventive effects of dietary Euglena on obesity in vivo. This study revealed that Euglena also has an important ameliorative effect on obesity and metabolic disorders, which laid a theoretical foundation for its future application in functional foods.

Spirulina Unleashed: A Pancreatic Symphony to Restore Glycemic Balance and Improve Hyperlipidemia and Antioxidant Properties by Transcriptional Modulation of Genes in a Rat Model

Hyperlipidemia is the root cause of numerous chronic conditions, leading to high mortality rates around the globe. Spirulina (Arthrospira platensis) microalgae serve as a promising reservoir of bioactive compounds with diverse pharmacological properties. The current study examined the nutritional profile of spirulina powder in relation to strict glycemic control, specifically focusing on its potential to lower lipid levels. In an in vivo investigation, normal healthy male Wistar albino rats (n = 60) were divided into two groups: a negative control group (NC) of ten rats and a high-fat diet group (n = 50) that were fed a cholesterol-rich diet until their cholesterol levels reached or exceeded 250 mg/dL. Subsequently, the hypercholesterolemic rats were then randomly allocated to several treatment groups: a positive control (PC); a standard treatment diet (STD) involving fenofibrate at a dose of 20 mg/kg body weight; and three experimental groups (T1, T2, and T3) that received spirulina powder supplementation at doses of 300, 600, and 900 mg per kg body weight, respectively, for the period of 12 weeks. Blood samples were analyzed for oxidative stress biomarkers, insulin levels, lipid profiles, liver function, and expression of gene levels in the diabetogenic pathway. The study utilized spectrophotometric colorimetric methods to identify oxidative stress biomarkers, serum kit methods to measure lipid profiles and liver enzymes, and the assessment of qPCR for mRNA quantity. According to the research findings, spirulina powder has certain noteworthy features. It had the greatest quantity of chlorogenic acid (4052.90 µg/g) among seven phenolics and two flavonoid compounds obtained by HPLC-UV analysis. Furthermore, the proximate analysis demonstrated that spirulina is high in protein (16.45 ± 0.8%) and has a significant energy yield of 269.51 K-calories per 100 g. A maximal spirulina dose of 900 mg/kg/wt significantly lowered oxidative stress, cholesterol, triglyceride, low-density lipoproteins (LDL), and insulin levels (p ≤ 0.05). In contrast, high-density lipoprotein (HDL) and total antioxidant capacity (TAC) levels increased significantly (p ≤ 0.05) compared to all other groups, except the NC group. The study provides remarkable proof about the pharmacological impact of spirulina powders. Significant reductions (p ≤ 0.05) in liver enzymes {alanine aminotransferase (ALT) and aspartate aminotransferase (AST)} were observed across all treatment groups, with the exception of the NC, compared to the positive control. The treatment groups had significantly greater gene expression levels of INS-1, PDX-1, IGF-1, and GLUT-2 than the positive control group (p ≤ 0.05). These findings highlight spirulina’s potential as a long-term regulator of hyperglycemia in rat models with induced hyperlipidemia, owing to its phenolic bioactive components that serve as antioxidants.

Fucosylated chondroitin sulfate alleviates diet-induced obesity by modulating intestinal lipid metabolism and colonic microflora

Fucosylated chondroitin sulfate from Pearsonothuria graeffei (FCS-Pg), a natural macromolecular polysaccharide, has been proven to prevent obesity, but its underlying molecular mechanism is still unclear. C57BL/6 J mice fed on high fat diet (HFD) were administered FCS-Pg lasting for ten weeks. The results demonstrated that FCS-Pg supplementation reduced body weight with dosage manner compared with HFD group. The expressions of intestinal lipid synthesis related proteins such as cluster of differentiation 36 (CD36) in FCS-Pg group were lower than those in the HFD group. Compared with the normal group, HFD caused gut microbiota disorder in the colon. FCS-Pg supplementation at high dosage restored the gut microbiota composition with higher abundance of Alistipes and Bacteroidetes and lower abundance of Colidextribacter, Bilophila and Firmicutes compared with HFD group. Moreover, FCS-Pg decreased the expression of proteins involved in triglyceride synthesis such as glycerol 3-phosphate dehydrogenase 1 (GPD1) and increased the expression of proteins involved in lipolysis and thermogenesis such as adipose triglyceride lipase (ATGL) and uncoupling protein 1 (UCP1) in the white adipose tissue (WAT) compared with HFD group. In conclusion, our study suggested that FCS-Pg significantly prevented obesity and improved WAT function in HFD-fed mice by regulating intestinal lipid metabolism and microflora composition.

Natural Honey Proteins Prevent Diet-Induced Obesity and Metabolic Disorders in Rats.

Previous studies have shown that oral whole honey reduces weight gain in rats on a normal diet (ND) or high-fat diet (HFD) and suppresses inflammation by modulating immunological cytokines in human neutrophils and macrophages. We hypothesize that the honey proteins (HP) are responsible for the reduced weight gain in rats on ND and HFD and that HP would alleviate obesity parameters. To test this, proteins were isolated from acacia honey through the salting-out method. Wistar rats (N = 24) were randomized to get ND or HFD for 4 weeks, then further randomized to four groups and treated with HP or saline for another 4 weeks. Energy intake (EI), body weight gain, EI per gram body weight gain, serum glucose, and lipids were measured. Expression of adipose tissue genes fatty acid binding protein (FABP), lipase C (LIPC), and apolipoprotein A-1 (APOA1) was evaluated through the quantitative polymerase chain reaction. HFD increased the body weight versus ND in weeks 1-4. HP for the next 4 weeks reduced weight gain in ND-HP and HFD-HP groups versus saline controls (P < .01). EI was not significantly different among groups. However, EI per gram body weight gain among groups was markedly different (P < .01), demonstrating reduced weight gain efficiency by HP (P < .01). HP reduced glucose in ND but not in HFD groups. Triglycerides were lower in both HP groups. The expressions of FABP, LIPC, and APOA1 genes were significantly increased (P < .05) in HP-treated HFD rats. Collectively, weight gain efficiency was remarkably reduced without altering EI in rats following the HP treatment, suggesting HP increased metabolic rate or substrate partitioning. Studies of HP are suggested in humans.

Retinal G-protein-coupled receptor deletion exacerbates AMD-like changes via the PINK1-parkin pathway under oxidative stress.

The intake of high dietary fat has been correlated with the progression of age-related macular degeneration (AMD), affecting the function of the retinal pigment epithelium through oxidative stress. A high-fat diet (HFD) can lead to lipid metabolism disorders, excessive production of circulating free fatty acids, and systemic inflammation by aggravating the degree of oxidative stress. Deletion of the retinal G-protein-coupled receptor (RGR-d) has been identified in drusen. In this study, we investigated how the RGR-d exacerbates AMD-like changes under oxidative stress, both invivo and invitro. Fundus atrophy became evident, at 12 months old, particularly in the RGR-d + HFD group, and fluorescence angiography revealed narrower retinal vessels and a reduced perfusion area in the peripheral retina. Although rod electroretinography revealed decreasing trends in the a- and b-wave amplitudes in the RGR-d + HFD group at 12 months, the changes were not statistically significant. Mice in the RGR-d + HFD group showed a significantly thinner and more fragile retinal morphology than those in the WT + HFD group, with disordered and discontinuous pigment distribution in the RGR-d + HFD mice. Transmission electron microscopy revealed a thickened Bruch's membrane along the choriocapillaris endothelial cell wall in the RGR-d + HFD mice, and the outer nuclear layer structure appeared disorganized, with reduced nuclear density. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated significantly lower levels of 25(OH)-vitamin D3 metabolites in the RGR-d + HFD group. Under oxidative stress, RGR-d localized to the mitochondria and reduced the levels of the PINK1-parkin pathway. RGR-d mice fed an HFD were used as a new animal model of dry AMD. Under high-fat-induced oxidative stress, RGR-d accumulated in the mitochondria, disrupting normal mitophagy and causing cellular damage, thus exacerbating AMD-like changes both invivo and invitro.

Shen-Bai-Jie-Du decoction suppresses the progression of colorectal adenoma to carcinoma through regulating gut microbiota and short-chain fatty acids

BackgroundShen-Bai-Jie-Du decoction (SBJDD), a traditional Chinese herb formula developed based on evidence-based medicine, is efficacy to reduce the recurrence and carcinogenesis of colorectal adenoma. However, the mechanism of SBJDD to treat colorectal adenoma remains unclear. The present study aims to investigate the efficacy and mechanism of SBJDD on colorectal adenoma carcinogenesis from the aspects of regulating gut microbiota and short-chain fatty acids (SCFAs).MethodsTwenty-one patients diagnosed with colorectal adenoma were recruited in the study and required to take SBJDD for four consecutive weeks. Analysis of gut microbiota was conducted using 16S rRNA gene amplicon sequencing, while levels of SCFAs in fecal and serum samples were determined through HPLC–MS/MS. Additionally, twenty-four Apcmin/+ mice were randomly assigned to normal diet (ND), high-fat diet (HFD), and SBJDD groups. The pharmacological effects and mechanism of SBJDD on colorectal adenoma carcinogenesis were assessed using RT-qPCR, HE staining, IHC staining, Western blot, IF staining, and Flow cytometry assays.ResultsOur clinical study has shown that SBJDD can regulate the gut microbiota composition and enhance SCFAs production in patients with colorectal adenoma. SBJDD alleviated colorectal adenoma formation and carcinogenesis, as well as protected the integrity of the intestinal barrier in the Apcmin/+ mice model compared to the HFD group. Additionally, SBJDD was found to regulate gut microbiota capable of producing SCFAs. G protein-coupled receptors GPR43, GPR41, and GPR109a were effectively activated in the SBJDD group, while HDAC1 and HDAC3 were inhibited. Furthermore, decreased expression levels of interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), along with elevated expression level of interleukin 10 (IL-10), were observed in the colorectal tissue of the SBJDD group. Finally, SBJDD exhibited the ability to reduce the proportion of M1-type macrophages while increasing the proportion of M2-type macrophages.ConclusionsOur study objectively demonstrated the pharmacological effects of SBJDD in inhibiting the progression of colorectal adenoma and investigated its mechanisms in terms of regulating gut microbiota, increasing SCFAs, and reducing colorectal inflammation.

The Anti-Inflammatory Effect of Lactococcus lactis-Ling-Zhi 8 on Ameliorating Atherosclerosis and Nonalcoholic Fatty Liver in High-Fat Diet Rabbits

Inflammation plays a crucial role in atherosclerosis and nonalcoholic fatty liver disease (NAFLD). We previously engineered a recombinant Lactococcus lactis strain expressing the Ling-Zhi immunomodulatory protein (L. lactis-LZ8). This study investigated the anti-atherosclerotic effects of L. lactis-LZ8 in rabbits fed a high-fat diet (HFD). Changes in body weight, serum lipid profiles, and liver function were monitored. The aorta and liver tissues were analyzed for gross pathology and histopathology. Eight-week administration of L. lactis-LZ8 with HFD ameliorated atherosclerosis by downregulating protein and gene expression associated with lipid metabolism and inflammation in the aortas. The rabbits receiving L. lactis-LZ8 exhibited a significant dose-dependent reduction in hepatic fat accumulation. RNA sequencing of the livers revealed that inflammatory genes in the L. lactis-LZ8 groups were downregulated compared to the HFD group. Disease ontology enrichment analysis indicated that these genes were involved in atherosclerosis. Gene set enrichment analysis plots revealed significant enrichment in the gene sets related to cholesterol homeostasis. CIBERSORT immune cell fraction analysis indicated significant infiltration by regulatory T cells, CD8+ T cells, activated dendritic cells, and natural killer cells in the L. lactis-LZ8 group. Our studies underscore LZ8’s role in precision nutrition, providing a potential solution to the current challenges in modifying atherosclerosis and NAFLD.

Highland Barley Alleviates High-Fat Diet-Induced Obesity and Liver Injury Through the IRS2/PI3K/AKT Signaling Pathway in Rats.

Objectives: Highland barley (HB) consumption offers numerous health benefits; however, its impact on glycolipid metabolism abnormalities induced by a high-fat diet remains unclear. Consequently, this study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HB in the context of obesity; Methods: Rats were fed either a high-fat diet (HFD) to induce obesity or a standard diet (SD) for six weeks. The rats in the HFD group were randomly assigned into five groups: HFD+HFD, HFD+SD, and low (30%), medium (45%), and high (60%) doses of the HB diet for an additional ten weeks. Analyses of serum lipid profiles, liver histology, transcriptomes, and untargeted metabolomes were conducted; Results: HB intake resulted in decreased weight gain, reduced feed intake, lower serum triglyceride and cholesterol levels, and diminished hepatic lipid accumulation. It also improved insulin and fasting blood glucose levels, and antioxidant capacity in the HFD-fed rats. Transcriptome analysis revealed that HB supplementation significantly suppressed the HFD-induced increase in the expression of Angptl8, Apof, CYP7A1, GDF15, Marveld1, and Nr0b2. Furthermore, HB supplementation reversed the HFD-induced decrease in Pex11a expression. Untargeted metabolome analysis indicated that HB primarily influenced the pentose phosphate pathway, the Warburg effect, and tryptophan metabolism. Additionally, integrated transcriptome and metabolome analyses demonstrated that the treatments affected the expression of genes associated with glycolipid metabolism, specifically ABCG8, CYP2C12, CYP2C24, CYP7A1, and IRS2. Western blotting confirmed that HB supplementation impacted the IRS2/PI3K/AKT signaling pathway; Conclusions: HB alleviates HFD-induced obesity and liver injury in an obese rat model possibly through the IRS2/PI3K/Akt signaling pathway.

Obesity-induced extracellular vesicles proteins drive the endometrial cancer pathogenesis: therapeutic potential of HO-3867 and Metformin.

Endometrial cancer (EC) is the leading gynecologic malignancy in the United States with obesity implicated in 57% of cases. This research investigates the molecular complexities of extracellular vesicles (EV) secretion as carriers of oncogenic protein and their involvement in obesity-mediated EC. An understanding of these mechanisms is pivotal for unraveling pathways relevant to obesity-associated EC, thereby guiding the development of innovative prevention and treatment strategies. Our exploration revealed a significant increase in EV secretion carrying oncogenic proteins (TMEM205, STAT5, and FAS) in adipose and uterine tissues/serum samples from obese EC patients compared to control (without cancer). We identified alterations in EV-regulating proteins (Rab7, Rab11, and Rab27a) in obesity-mediated EC patients, adipose/uterine tissues, and serum samples. Through a 24-week analysis of the effects of a 45% kcal high-fat diet (HFD) on mice, we observed increased body weight, increased adipose tissue, enlarged uterine horns, and increased inflammation in the HFD group. This correlated with elevated levels of EV secretion and increased expression of oncogenic proteins TMEM205, FAS, and STAT5 and downregulation of the tumor suppressor gene PIAS3 in adipose and uterine tissues. Furthermore, our study confirmed that adipocyte derived EV increased EC cell proliferation, migration and xenograft tumor growth. Additionally, we identified that the small molecule inhibitors (HO-3867) or Metformin inhibited EV secretion in vitro and in vivo, demonstrating significant inhibition of high glucose or adipocyte-mediated EC cell proliferation and a reduction in body weight and adipose tissue accumulation when administered to HFD mice. Moreover, HO-3867 or Metformin treatment inhibited HFD induced hyperplasia (precursor of EC) by altering the expression of EV-regulated proteins and decreasing oncogenic protein expression levels. This study provides critical insights into the mechanisms underpinning obesity-mediated EV secretion with oncogenic protein expression, shedding light on their role in EC pathogenesis. Additionally, it offers pre-clinical evidence supporting the initiation of novel studies for EV-targeted therapies aimed at preventing obesity-mediated EC.

Curcumin Modulates the Differential Effects of Fructose and High-Fat Diet on Renal Damage, Inflammation, Fibrosis, and Lipid Metabolism.

Dyslipidemia and obesity hypercaloric diet-induced lead to kidney damage. We investigated the effect of curcumin on the expression of proteins related to inflammation, fibrosis, fatty acids metabolism, kidney damage, and morphological changes in the kidneys of mice hypercaloric diets-fed. Groups of 5-week-old C57BL/6 mice (n=6) were formed: Control (C), High-fructose diet (F), Highfructose diet and curcumin (F+Cur), High-fat diet (HFD), High-fat diet and curcumin (HFD+Cur), High-fat diet and fructose (HFD+F), High-fat diet, fructose and curcumin (HFD+F+Cur), treated for 16 weeks with 30% (w/v) fructose, 60% (w/w) fat and 0.75% (w/w) curcumin. Kidneys were obtained for histomorphological and Western Blot analysis. Curcumin prevented TNF-α overexpression in the F and HFD+F groups. VLCAD expression was higher in the F, HFD, and HFD+F groups. PPARγ expression was lower in the F+Cur, HFD+Cur, and HFD+F+Cur groups. Curcumin prevented overexpression of CPT1 and KIM1 in the HFD+F and HFD groups. Curcumin prevented morphological lesions, fibrosis, and lipid deposition that were hypercaloric diet-induced. Chronic consumption of hypercaloric diets causes inflammation, fibrosis, and lipid deposition in the kidney. It is suggested that curcumin prevents renal structural damage, limits tissue lipid deposition, and differentially modulates renal injury depending on diet composition in mice fed high-fat and/or high-fructose diets.

Acupoint catgut embedding: a potential intervention strategy for obesity-related precocious puberty.

Obesity-related precocious puberty is induced by obesity, and acupoint catgut embedding (ACE) therapy is known to treat obesity. This study aims to validate the hypothesis that ACE can delay the onset of obesity-related precocious puberty. Female Sprague-Dawley rats, 21 days old, were randomly divided into three groups: the high-fat diet combined with ACE treatment group (ACE), the high-fat diet group (HFD), and the normal control diet group (NCD), with 8 rats in each group. The vaginal opening (VO) time was monitored, and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total estradiol (E2) were measured, followed by statistical analysis. Kaplan-Meier survival curves, with VO as the endpoint, showed that vaginal opening was delayed in the ACE group compared to the HFD group, with a statistically significant difference (p < 0.05). The changes in levels of FSH, LH, and E2 indicated that sexual development was delayed in the ACE group compared to the HFD group and was more similar to the NCD group. Combining the vaginal opening time and changes in hormone levels, this study confirms the potential role of ACE in delaying the onset of obesity-related precocious puberty.

The impact of vitamin D3 administration and of high fat diet on oxidative stress and inflammation in experimentally induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is commonly associated with obesity and may be exacerbated by the lack of vitamin D3. The study aimed to investigate the effects of vitamin D3 administration in female rats with PCOS and prolonged high fat diet (HFD). Forty-four female Wistar rats, 180-200 g, 10 weeks old, were randomly allocated into 2 groups (n=22) that received a single dose intramuscular injection of: sesame oil (group I), or estradiol valerate (5 mg) in sesame oil (group II). After 4 weeks, intraovarian cysts developed in group II, as evidenced by ultrasonography. In the next step, half of rats from each group received standard diet (SD) and the other half high fat diet, through oral gavage, for 17 weeks, the following groups being obtained: Control (SD), HFD, PCOS (PCOS+SD) and PCOS+HFD. Next, all the rats received, for 5 weeks, 500 UI/kg/day vitamin D3, through oral gavage. Lipid peroxidation was assessed through malondialdehyde level in the ovary and periovarian tissue and the inflammation was quantified in ovary by NFkB, pNFkB, NRF2 and SOD1 expressions. Ovaries from all groups were collected for histopathological analysis. Blood samples were taken to evaluate the basal insulin, triglycerides and total cholesterol levels throughout the experiment. Both groups with PCOS recorded significant increases of malondialdehyde in ovaries (p<0.001) and in periovarian tissue, especially in PCOS+HFD (p<0.05), even after vitamin D3 administration. PCOS+HFD group treated with vitamin D3 showed a high degree of inflammation in ovarian histopathology but with decreased pNFkB expression (p<0.01) while PCOS group recorded an increased SOD1 expression (p<0.05). Additionally, vitamin D3 treatment attenuated the insulin level (p<0.001) in PCOS and in HFD groups and the total cholesterol level in PCOS+HFD group, but triglycerides recordings were without statistical significance (p>0.05). HFD induced inflammation in ovaries, evidenced histologically and through increases of COX2 expressions (p<0.05) without significant influences on oxidative stress and on cholesterol levels. Polycystic ovary syndrome is associated with oxidative stress and inflammation in the ovary tissue and in blood with increased levels of insulin, total cholesterol and triglycerides that might be partially mitigated by vitamin D3 oral administration.

Aerobic Exercise Prevents High-Fat-Diet-Induced Adipose Tissue Dysfunction in Male Mice

Background/Objectives: This study aimed to assess the effect of aerobic exercise on capillary density and vascular smooth muscle cell (VSMC) phenotype in the visceral and subcutaneous adipose tissue of high-fat-diet (HFD) mice in order to understand the mechanisms underlying improvements in insulin resistance (IR) and chronic inflammation in adipose tissue (AT). Methods: Male C57BL/6J mice were divided into HFD and normal diet groups for 12 weeks and then further split into sedentary and aerobic exercise subgroups for an additional 8 weeks. Various parameters including body weight, fat weight, blood glucose, lipid profile, insulin levels, glucose tolerance, and inflammatory cytokines were evaluated. Results: Aerobic exercise reduced HFD-induced weight gain, IR, and improved lipid profiles. HFD had a minimal effect on inflammatory cytokines except in visceral adipose tissue (VAT). IR was associated with capillary density in subcutaneous adipose tissue (SAT) and VSMC phenotype in VAT. Aerobic exercise promoted anti-inflammatory responses in VAT, correlating with VSMC phenotype in this tissue. Conclusions: Aerobic exercise can alleviate HFD-induced IR and inflammation through the modulation of VSMC phenotype in AT.

Investigating the Hepatic Response to Orlistat and White Tea in Rats on a High-Fat Diet.

High-fat diets have detrimental health impacts that increase the likelihood of developing obesity and metabolic syndrome. This study aimed to examine the potential antioxidant and anti-inflammatory effects of orlistat and white tea in rats fed a high-fat diet. Thirty-two rats were randomized into four groups: control (standard diet), HFD (high-fat diet), HFD+Orlistat (high-fat diet+orlistat), and HFD+WT (high-fat diet+white tea extract). A significant increase in malondialdehyde (MDA) levels and a decrease in total thiol (TT) levels were detected in the HFD group (p < 0.001). On the other hand, a decrease in the MDA level (p < 0.001) and an increase in the TT level were observed in the orlistat and white tea groups compared with those in the HFD group (p < 0.001). Histopathological examinations revealed that, compared with the HFD alone, orlistat and white tea reduced fat accumulation, prevented degenerative changes in hepatocytes, and decreased the histopathological damage score (p = 0.001). Immunohistochemical examinations of nuclear factor-kappa B (NF-kB/p65) revealed that compared with the HFD, orlistat and white tea reduced immunopositivity (p = 0.001). White tea decreases lipid peroxidation and oxidative stress. Both white tea and orlistat decreased fat formation and inflammation in the liver and regulated inflammation by reducing Nf-kB positivity. Nevertheless, further research is needed to assess their impact on human subjects.

Inhibition of HDAC6 mitigates high-fat diet-induced kidney inflammation and hypertension via reduced infiltration of macrophages

Obesity-mediated hypertension is a worldwide problem. Recent research has indicated that chronic inflammation is associated with the pathogenesis of obese hypertension. Activated immune cells infiltrate target organs, such as arteries, kidneys, and brain, causing end-organ damage and hypertension. Histone deacetylase 6 (HDAC6) regulates the inflammatory cell activity mediating the production of inflammatory cytokines and may play a role in the crosstalk between inflammation and hypertension. In this study, we investigated the roles of HDAC6 in high-fat diet (HFD)-induced kidney inflammation and hypertension. Nine-week-old male C57BL/6 mice were fed either a normal diet (ND) or HFD for 15 weeks. HFD-induced hypertension with increased HDAC6 activities in the kidney and bone marrow-derived macrophages (BMDM). When HFD group reached the hypertensive phase, each group of mice was intraperitoneally injected with vehicle or selective HDAC6 inhibitor Tubacin (1 mg/kg/day) for 14 days. Tubacin treatment lowered blood pressure (BP) of HFD-fed mice to the normal level with successful inhibition of HDAC6 activity. Immunohistochemical staining of F4/80, which is known as a macrophage marker, revealed that HFD promoted macrophage infiltration into the kidney. Consequently, pro-inflammatory factors TNFα and IL-6 gene expressions in the kidney were increased by HFD. Tubacin canceled HFD-induced macrophage infiltration and inflammation in the kidney. HDAC6 gene silencing and Tubacin treatment in Raw 264.7 cells also blocked the chemoattractant-stimulated cell migration in vitro. The results reveal the novel role of HDAC6 in BMDM migration, kidney inflammation, and high BP induced by HFD providing HDAC6 inhibitors as a therapeutic option for obesity-mediated hypertension.

7769 Natural plant extract alleviates high-fat diet-induced obesity through enhancing PLIN5 expression

Abstract Disclosure: S. Shin: None. H. Jang: None. E. Kwon: None. Obesity is one of the metabolic diseases caused by excessive differentiation and excessive accumulation of adipose tissue due to an imbalance between energy intake and consumption. Various drugs have been developed to effectively treat obesity, but the side effects often outweigh the benefits. Therefore, alternative weight loss supplements that can minimize side effects are needed. In this study, the effects of natural plant extract (NPE) on the high-fat diet (HFD)-induced obesity mice were confirmed to discover new anti-obesity material.After acclimating C57BL/6J mice for 1 week, they were divided into two groups: a normal diet (ND) group and an HFD group. After inducing obesity over 4 weeks, the HFD group was divided into HFD and HFD+NPE and reared together with the ND group for an additional 10 weeks. After a 12-hour fasting period, observations were made on weight, adipose tissue mass, morphological changes in adipocytes, and the expression differences in genes and proteins related to fatty acid oxidation (FAO) in the epididymal white adipose tissue, particularly focusing on the PLIN5 protein.The increase in body weight and epididymal fat mass induced by the HFD was reduced by the administration of NPE. Morphological analysis of the epididymal fat revealed a significant increase in adipocyte size in the HFD group, whereas the NPE group showed a reduction in adipocyte size. The expression of FAO-related genes (PPARa, PGC1a, CPT1, and CPT2) and TCA cycle-related genes (PDHb, ACO, DIST, SUCLG, SDHC, and MDH2) decreased in the epididymal fat due to the HFD, but significantly increased with the administration of NPE. The NPE induced the breakdown of intracellular stored triglycerides by upregulating ATGL, LIPE, and MGL mRNA expression. The resulting liberated fatty acids were translocated to the mitochondria and oxidized through the TCA cycle, ultimately leading to a reduction in body fat. Furthermore, PLIN5 expression exhibited a significantly higher level in the NPE group compared to the other two groups. In other words, elevation in PLIN5 expression, induced by the NPE, appears to enhance lipid breakdown, activate FAO pathways, and stimulate the TCA cycle. Consequently, lipid combustion is increased, improving the weight gain and fat accumulation induced by the HFD.If additional experimental results on human application align with the above findings, NPE holds the potential as a low-side-effect ingredient for weight loss supplements. Presentation: 6/1/2024

High-fat diet-induced obesity exacerbated collagenase-induced tendon injury with upregulation of interleukin-1beta and matrix metalloproteinase-1

ABSTRACT Aims Obesity increases tendinopathy’s risk, but its mechanisms remain unclear. This study examined the effect of high-fat diet (HFD)-induced obesity on the outcomes and inflammation of collagenase-induced (CI) tendon injury. Methods Mice were fed with standard chow (SC) or HFD for 12 weeks. Bacterial collagenase I or saline was injected over the patellar tendons of each mouse. At weeks 2 and 8 post-injection, the patellar tendons were harvested for histology, immunohistochemical staining, and gait analysis. The difference (Δ) of limb-idleness index (LII) at the time of post-injury and pre-injury states was calculated. Biomechanical test of tendons was also performed at week 8 post-injection. Results HFD aggravated CI tendon injury with an increase in vascularity and cellularity compared to SC treatment. The histopathological score (week 2: p = 0.025; week 8: p = 0.013) and ΔLII (week 2: p = 0.012; week 8: p = 0.005) were significantly higher in the HFD group compared to those in the SC group after CI tendon injury. Stiffness (saline: p = 0.003; CI: p = 0.010), ultimate stress (saline: p < 0.001; CI: p = 0.006), and Young’s modulus (saline: p = 0.017; CI: p = 0.007) were significantly lower in the HFD group compared to the SC group at week 8 after saline or collagenase injection. HFD induced higher expression of IL-1β (week 2: p = 0.010; week 8: p = 0.025) and MMP-1 (week 2: p = 0.010; week 8: p = 0.004) compared to SC treatment after CI tendon injury at both time points. Conclusions HFD-induced obesity exacerbated histopathological, functional, and biomechanical changes in the CI tendon injury model, which was associated with an upregulation of IL-1β and MMP-1.