Reduced Fat Accumulation Research Articles

Integrated Analysis of Transcriptome and Metabolome Provides Insight into Camellia oleifera Oil Alleviating Fat Accumulation in High-Fat Caenorhabditis elegans.

Camellia oil (CO) is a high medicinal and nutritional value edible oil. However, its ability to alleviate fat accumulation in high-fat Caenorhabditis elegans has not been well elucidated. Therefore, this study aimed to investigate the effect of CO on fat accumulation in high-fat C. elegans via transcriptome and metabolome analysis. The results showed that CO significantly reduced fat accumulation in high-fat C. elegans by 10.34% (Oil Red O method) and 11.54% (TG content method), respectively. Furthermore, CO primarily altered the transcription levels of genes involved in longevity regulating pathway. Specifically, CO decreased lipid storage in high-fat C. elegans by inhibiting fat synthesis. In addition, CO supplementation modulated the abundance of metabolic biomarkers related to pyrimidine metabolism and riboflavin metabolism. The integrated transcriptome and metabolome analyses indicated that CO supplementation could alleviate fat accumulation in high-fat C. elegans by regulating retinol metabolism, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, ascorbate and aldarate metabolism, and pentose and glucuronate interconversions. Overall, these findings highlight the potential health benefits of CO that could potentially be used as a functional edible oil.

Zanthoxylum bungeanum amides ameliorates nonalcoholic fatty liver via regulating gut microbiota and activating AMPK/Nrf2 signaling

Ethnopharmacological relevanceZanthoxylum bungeanum Maxim. (Rutaceae) is a known herbal medicine with various bioactivities, including anti-obesity, lipid-lowering, learning & memory improving and anti-diabetes, and amides in Z. bungeanum (AZB) are considered as the major active agents for its bioactivities. Aim of the studyThis research was carried out to uncover the anti-NAFL effect of AZB and its corresponding molecular mechanisms. MethodsThe central composite design-response surface methodology (CCD-RSM) was utilized to optimize the AZB extraction process, and the anti-NAFL effect of AZB was investigated on high fat diet (HFD) fed mice (HFD mice). The levels of ROS in liver tissues were determined using laser confocal microscopy with DCFH-DA probe staining, and anti-enzymes (such as HO-1, SOD, CAT & GSH-PX) and MDA in liver tissues were measured using commercial detecting kits. GC-MS was used to determine the short-chain fatty acids (SCFAs) contents in feces and blood of mice. 16S high-throughput sequencing, western blotting (WB) assay and immunofluorescence (IF) were used to explore the intestinal flora changes in mice and the potential mechanisms of AZB for treatment of NAFL. ResultsOur results showed AZB reduced body weight, alleviated liver pathological changes, reduced fat accumulation, and improved oxidative stress in HFD mice. In addition, we also found AZB improved OGTT and ITT, reduced TG, TC, LDL-C, whereas increased HDL-C in HFD mice. AZB increased total number of the species and interspecies kinship of gut microbiota and reduced the richness and diversity of gut microbiota in HFD mice. Moreover, AZB decreased the ratio of Firmicutes/Bacteroidota, whereas increased the abundance of Allobaculum, Bacteroides and Dubosiella in feces of HFD-fed mice. Furthermore, AZB increased the production of SCFAs, and up-regulated the phosphorylation of AMPK and increased the nuclear transcription of Nrf2 in liver of HFD mice. ConclusionCollectively, our results suggested AZB can improve NAFL, which could reduce body weight, reverse liver lesions and fat accumulation, improve oxidative stress in liver tissues of HFD mice. Furthermore, the mechanisms are related to increase of the abundance of high-producing bacteria for SCFAs (e.g. Allobaculum, Bacteroides and Dubosiella) to activate AMPK/Nrf2 signaling.

1599-P: Regulation of Mitochondrial Dynamics Ameliorates Hepatic Steatosis through TFEB Activation

Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver disease that is closely related to metabolic syndromes, obesity, and type 2diabetes. There is strong evidence that mitochondrial dysfunction plays a significant role in the development and progression of NAFLD. Recently, growing evidence suggests that the TFEB plays a pivotal role in mitochondrial dynamics. In this study, we investigated that mitochondrial dynamics play the potential role and mechanisms of TFEB in the amelioration of NAFLD. FFA increased expression of mitochondrial fission proteins p-Drp1, Fis1 and decreased expression of fusion proteins OPA1, Mfn2 and inhibition of TFEB activation. Mitotracker stain significantly increased in the proportion of cells with fragmented mitochondria in FFA-treated cells. HFD-fed mice displayed histology consistent with pathological hepatic steatosis. EM analysis indicated that HFD-fed mitochondria tended to be shorter and more round than ND-fed mitochondria. Western blot analyses reveal increased expression of the fission proteins, p-Drp1, Fis1, and significantly decreased in the fusion protein, Mfn2 and OPA1 in HFD-fed group. In vivo Tfeb knockout dramatically increased hepatic fat accumulation, liver ballooning in HFD-fed mice. EM analysis showed that HFD-fed Tfeb knockout mice had more rounded and swollen mitochondria, indicating that TFEB was dependent on the regulation of mitochondrial fragmentation. In vivo Tfeb knockout reveal significantly increased expression of the fission proteins in HFD-fed group. To demonstrated the direct regulatory mechanism of mitochondrial dynamics and TFEB activation, we used siRNA DRP1 and Mdivi-1. Inhibition of Drp1 promotes mitochondrial fusion, increased expression of fusion protein and reduced fat accumulation and activated TFEB. These results suggest a role in improving hepatic steatosis through regulation of TFEB-mediated mitochondrial dynamics in NAFLD. Disclosure J.Yoo: Other Relationship; American Diabetes Association. Y.Hwang: None. Funding National Research Foundation of Korea (2022R1I1A1A01069899)

1636-P: The Effects of MS-275 Derivative in Diabetic Skeletal Muscle Atrophy

Aim/hypothesis: Histone Deacetylase (HDAC) is considered one of the pathogenic factors that induced muscle atrophy. MS-275, HDAC inhibitor, plays an important role in many physiological processes, and includes muscle contraction, mitochondrial metabolism, and decision of cell fate. Recently it was reported MS275 prevented insulin resistance and obesity. However, the effects of MS-275 derivative in diabetic skeletal muscle atrophy have not been well studied. In this study, we investigated the preventive effects of MS-275 derivative in diabetic muscle atrophy using db/db mice. Method: To investigate the effects of MS-275 derivative on diabetic muscle atrophy, db/db mice were randomly divided into three groups: control group, db/db group, and db/db plus MS-275 derivative group. The mice were administered MS-275 derivative (7 mg/kg/i.p) for 4 weeks. The H&E stained sections were measured for cross-sectional area analyses using Image J software. To investigate the molecular mechanisms of MS-275 derivative, several factors related with muscle atrophy were tested using RT-PCR. Results: Administration of MS-275 derivative to db/db mice suppressed muscle weight loss and insulin resistance. As a result of examining muscle mass and fat accumulation in the hindlimb by MRI, we found MS-275 derivative reduced fat accumulation and improved muscle loss. Tibialis anterior (TA) muscle and gastrocnemius (GA) muscle had significantly induced muscle atrophy in db/db mice. However, treatment with MS-275 derivative prevented weight loss of TA and GA muscles and it also recovered reduction of muscle fiber size. Interestingly, MS-275 derivative dramatically reduced atrophy related gene expressions in TA muscle. Conclusion: In this study, MS-275 derivative ameliorated muscle atrophy through a reduction of atrophy related gene expressions in db/db mice. These results suggest MS-275 derivative may be a basis for the development of therapeutic drugs as applied to atrophy-related muscular or metabolic diseases. Disclosure N.Lee: None. H.Kim: None. T.Kim: None. S.An: None. K.Lee: None. Y.Kim: None. S.Choi: None. Y.Kim: None. Y.Son: None. S.Choi: None. Y.Y.Kang: None. J.Jeon: None. S.Han: None.

Dapagliflozin prevents abdominal visceral and subcutaneous adipose tissue dysfunction in the insulin-resistant canine model.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) promote urinary glucose excretion, induce weight loss, and reduce fat accumulation. The effects of the SGLT2i dapagliflozin (DAPA) on subcutaneous (SC) and visceral (VIS) adipose tissue function remain unclear. The objective of this study is to evaluate SC and VIS adipose tissue function in an insulin-resistant canine model. A total of 12 dogs were fed a high-fat diet (HFD) for 6 weeks and thenwere given a single low dose of streptozotocin (18.5 mg/kg) to induce insulin resistance. Animals were then randomized and exposed to DAPA (n = 6, 1.25 mg/kg) or placebo (n = 6) once per day for 6 weeks while remaining on the HFD. DAPA prevented further weight gain induced by the HFD and normalized fat mass. DAPA reduced fasting glucose and increased free fatty acids, adiponectin, and β-hydroxybutyrate. DAPA reduced adipocyte diameter and cell distribution. Furthermore, DAPA increased genes associated with beiging, lipolysis, and adiponectin secretion and the expression of the adiponectin receptor ADR2, in SC and VIS adipose tissue. DAPA increased AMP-activated protein kinase activity and maximal mitochondrial respiratory function, especially in the SC depot. Furthermore, DAPA reduced cytokines and ceramide synthesis enzymes in SC and VIS depots. For the first time, to our knowledge, we identify mechanisms by which DAPA enhances adipose tissue function in regulating energy homeostasis in an insulin-resistant canine model.

Anti-Adipogenic Activity of Secondary Metabolites Isolated from Smilax sieboldii Miq. on 3T3-L1 Adipocytes.

Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. To evaluate the anti-obesity effects of S. sieboldii (Smilacaceae), we screened methylene chloride (CH2Cl2), ethyl acetate (EtOAc), aqueous-saturated n-butanol, and ethanol (EtOH) extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes. The 3T3-L1 cell line with Oil red O staining with the help of fluorometry was used as an indicator of anti-obesity activity. Bioactivity-guided fractionation of the EtOH extract and subsequent phytochemical investigation of the active CH2Cl2- and EtOAc-soluble fractions resulted in the isolation of 19 secondary metabolites (1-19), including a new α-hydroxy acid derivative (16) and two new lanostane-type triterpenoids (17 and 18). The structures of these compounds were characterized using various spectroscopic methods. All the isolated compounds were screened for adipogenesis inhibition at a concentration of 100 μM. Of these, compounds 1, 2, 4-9, 15, and 19 significantly reduced fat accumulation in 3T3-L1 adipocytes, especially compounds 4, 7, 9, and 19, showing 37.05 ± 0.95, 8.60 ± 0.41 15.82 ± 1.23, and 17.73 ± 1.28% lipid content, respectively, at a concentration of 100 μM. These findings provide experimental evidence that isolates from S. sieboldii extracts exert beneficial effects regarding the regulation of adipocyte differentiation.

Pyrroloquinoline-quinone to reduce fat accumulation and ameliorate obesity progression.

Obesity is a major health concern worldwide, and its prevalence continues to increase in several countries. Pyrroloquinoline quinone (PQQ) is naturally found in some foods and is available as a dietary supplement in its disodium crystal form. The potential health benefits of PQQ have been studied, considering its antioxidant and anti-inflammatory properties. Furthermore, PQQ has been demonstrated to significantly influence the functions of mitochondria, the organelles responsible for energy production within cells, and their dysfunction is associated with various health conditions, including obesity complications. Here, we explore PQQ properties that can be exploited in obesity treatment and highlight the underlying molecular mechanisms. We review animal and cell culture studies demonstrating that PQQ is beneficial for reducing the accumulation of visceral and hepatic fat. In addition to inhibiting lipogenesis, PQQ can increase mitochondria number and function, leading to improved lipid metabolism. Besides diet-induced obesity, PQQ ameliorates programing obesity of the offspring through maternal supplementation and alters gut microbiota, which reduces obesity risk. In obesity progression, PQQ mitigates mitochondrial dysfunction and obesity-associated inflammation, resulting in the amelioration of the progression of obesity co-morbidities, including non-alcoholic fatty liver disease, chronic kidney disease, and Type 2 diabetes. Overall, PQQ has great potential as an anti-obesity and preventive agent for obesity-related complications. Although human studies are still lacking, further investigations to address obesity and associated disorders are still warranted.

Precedence of Bone Loss Accompanied with Changes in Body Composition and Body Fat Distribution in Patients with Type 2 Diabetes Mellitus

A total of 596 patients with T2DM, including 308 male and 288 female patients, were included in the follow-up study; the median follow-up time was 2.17 years. We calculated the difference between the endpoint and the baseline of each body composition index and the annual rate. The research participants were divided into the increased body mass index (BMI) group, stable BMI group, and decreased BMI group. Some confounding factors were adjusted, such as BMI, fat mass index (FMI), muscle mass index (MMI), muscle/fat mass ratio (M/F), trunk fat mass index (TFMI), appendicular skeletal muscle mass index (ASMI), and appendicular skeletal muscle mass/trunk fat mass ratio (A/T). The linear analysis showed that ΔFMI and ΔTFMI were negatively correlated with the change in femoral neck BMD (ΔFNBMD) and ΔMMI, ΔASMI, ΔM/F, and ΔA/T were positively correlated with ΔFNBMD. The risk of FNBMD reduction in patients with increased BMI was 56.0% lower than that in patients with decreased BMI; also, the risk in patients with stable M/F was 57.7% lower than that in patients with decreased M/F. The risk in the A/T increase group was 62.9% lower than that in the A/T decrease group. A reasonable muscle/fat ratio is still beneficial to maintaining bone mass. Maintaining a certain BMI value is conducive to maintaining FNBMD. Simultaneously, increasing the proportion of muscle mass and reducing fat accumulation can also prevent FNBMD loss.

Adipose Tissue Remodeling in Obesity: An Overview of the Actions of Thyroid Hormones and Their Derivatives.

Metabolic syndrome and obesity have become important health issues of epidemic proportions and are often the cause of related pathologies such as type 2 diabetes (T2DM), hypertension, and cardiovascular disease. Adipose tissues (ATs) are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. An ample body of evidence indicates that in some pathophysiological conditions, the aberrant remodeling of adipose tissue may provoke dysregulation in the production of various adipocytokines and metabolites, thus leading to disorders in metabolic organs. Thyroid hormones (THs) and some of their derivatives, such as 3,5-diiodo-l-thyronine (T2), exert numerous functions in a variety of tissues, including adipose tissues. It is known that they can improve serum lipid profiles and reduce fat accumulation. The thyroid hormone acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein 1 (UCP1) to generate heat. Multitudinous investigations suggest that 3,3',5-triiodothyronine (T3) induces the recruitment of brown adipocytes in white adipose depots, causing the activation of a process known as "browning". Moreover, in vivo studies on adipose tissues show that T2, in addition to activating brown adipose tissue (BAT) thermogenesis, may further promote the browning of white adipose tissue (WAT), and affect adipocyte morphology, tissue vascularization, and the adipose inflammatory state in rats receiving a high-fat diet (HFD). In this review, we summarize the mechanism by which THs and thyroid hormone derivatives mediate adipose tissue activity and remodeling, thus providing noteworthy perspectives on their efficacy as therapeutic agents to counteract such morbidities as obesity, hypercholesterolemia, hypertriglyceridemia, and insulin resistance.

Tussilagone ameliorates high-fat diet-induced hepatic steatosis by enhancing energy metabolism and antioxidant activity.

Non-alcoholic fatty liver disease (NAFLD) is a major health problem. However, no effective treatments are currently available. Thus, there is a critical need to develop novel drugs that can prevent and treat NAFLD with few side effects. In this study, Tussilagone (TUS), a natural sesquiterpene isolated from Tussilago farfara L, was explored in vitro and in vivo for its potential to treat NAFLD. Our results showed that in vitro TUS reduced oleic acid palmitate acid-induced triglyceride and cholesterol synthesis in HepG2cells, reduced intracellular lipid droplet accumulation, improved glucose metabolism disorders and increased energy metabolism and reduced oxidative stress levels. In vivo, TUS significantly reduced fat accumulation and improved liver injury in high-fat diet (HFD)-induced mice. TUS treatment significantly increased liver mitochondrial counts and antioxidant levels compared to the HFD group of mice. In addition, TUS was found to reduce the expression of genes involved in lipid synthesis sterol regulatory element binding protein-1 (SREBP1), fatty acid synthase (FASN), and stearoy-CoA desaturase 1 (SCD1) in vitro and in vivo. Our results suggest that TUS may be helpful in the treatment of NAFLD, suggesting that TUS is a promising compound for the treatment of NAFLD. Our findings provided novel insights into the application of TUS in regulating lipid metabolism.

MPEP Attenuates Intrahepatic Fat Accumulation in Obese Mice.

The blockade of metabotropic glutamate receptor type 5 (mGluR5) was previously found to reduce fat accumulation in HEPG2 cells. Here, we evaluated the effects of mGluR5 blockade in a mouse model of steatosis. Male ob/ob mice fed a high-fat diet were treated with MPEP or vehicle. After 7 weeks, liver biopsies were collected, and nuclei were isolated from fresh tissue. Lipid droplet area and collagen deposition were evaluated on tissue slices; total lipids, lipid peroxidation, and ROS were evaluated on tissue homogenates; PPARα, SREBP-1, mTOR, and NF-κB were assayed on isolated nuclei by Western Blot. Target genes of the above-mentioned factors were assayed by RT-PCR. Reduced steatosis and hepatocyte ballooning were observed in the MPEP group with respect to the vehicle group. Concomitantly, increased nuclear PPARα and reduced nuclear SREBP-1 levels were observed in the MPEP group. Similar trends were obtained in target genes of PPARα and SREBP-1, Acox1 and Acc1, respectively. MPEP administration also reduced oxidative stress and NF-κB activation, probably via NF-κB inhibition. Levels of common markers of inflammation (Il-6, Il1β and Tnf-α) and oxidative stress (Nrf2) were significantly reduced. mTOR, as well as collagen deposition, were unchanged. Concluding, MPEP, a selective mGluR5 negative allosteric modulator, reduces both fat accumulation and oxidative stress in a 7-week murine model of steatosis. Although underlying mechanisms need to be further investigated, this is the first in vivo study showing the beneficial effects of MPEP in a murine model of steatosis.

Flowers of Allium cepa L. as Nutraceuticals: Phenolic Composition and Anti-Obesity and Antioxidant Effects in Caenorhabditis elegans.

Allium cepa L., commonly known as onion, is one of the most-consumed vegetables. The benefits of the intake of its bulb are well studied and are related to its high polyphenol content. The flowers of onions are also edible; however, there are no studies about their biological properties. Our aim was to determine the polyphenolic profile and assess the antioxidant and anti-obesity capacity of an ethanolic extract from fresh flowers of A. cepa. The phenolic constituents were identified through LC-DAD-ESI/MSn. For the anti-obesity potential, the inhibitory activity against digestive enzymes was measured. Several in vitro assays were carried out to determine the antioxidant capacity. A Caenorhabditis elegans model was used to evaluate the effect of the extract on stress resistance and fat accumulation. For the first time, kaempferol and isorhamnetin glucosides were identified in the flowers. The extract reduced fat accumulation in the nematode and had a high lipase and α- glucosidase inhibitory activity. Regarding the antioxidant activity, the extract increased the survival rate of C. elegans exposed to lethal oxidative stress. Moreover, the activities of superoxide dismutase and catalase were enhanced by the extract. Our results demonstrate, for the first time, the antioxidant and anti-obesity activity of onion flowers and their potential use as functional foods and nutraceuticals.

A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5+) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5+, or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5+ administration significantly reduced lipids' accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5+ inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5+ significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5+ may be able to counteract adipogenesis and then obesity by inducing fat browning.

Dietary Fat Saturation and Endurance Exercise Alter Lipolytic Sensitivity of Adipocytes Isolated from Yucatan Miniature Swine , ,

This study examined the effects of dietary fat saturation and endurance exercise on lipolytic sensitivity of adipocytes isolated from Yucatan miniature swine. Twenty-four female swine had free access to a high fat diet with a polyunsaturated to saturated fat ratio (P:S) of 0.3 or 1.0, and were treadmill-exercised or remained sedentary. After 3 months, biopsies were taken, adipocytes were isolated and lipolytic activity was determined. Adipocytes were incubated with adenosine deaminase followed by epinephrine, isoproterenol, or epinephrine plus phenylisopropyladenosine, and glycerol release was measured. Backfat thickness was measured by ultrasonography. Our findings revealed that 1) adipocytes from 1.0 P:S diet-fed swine released 30% more glycerol than adipocytes from 0.3 P:S diet-fed swine when stimulated by 1 micromol/L isoproterenol; 2) adipocytes from exercised swine released 45% more glycerol than adipocytes from sedentary swine when stimulated by 1 micromol/L epinephrine; 3) body weight of exercised swine was significantly lower than sedentary swine; and 4) backfat thickness was less in exercised swine than in sedentary swine (2.39 vs. 2.95 cm, P = 0.002). We conclude that ad libitum consumption of diet with a P:S of 1.0, combined with endurance exercise, increases lipolytic sensitivity, lowers body weight gain, and reduces fat accumulation in female Yucatan miniature swine.

Beneficial Effects of ε-Viniferin on Obesity and Related Health Alterations

Viniferin is a phenolic compound belonging to the group of stilbenoids. In particular, ε-viniferin is a dimer of resveratrol, found in many plant genders, among which grapes (Vitis vinifera) are a primary source. Due to the fact that ε-viniferin is mainly present in the woody parts of plants, their use as a source of this bioactive compound is a very interesting issue in a circular economy. Both, in vitro studies carried out in pre-adipocytes and mature adipocytes and in vivo studies addressed in mice show that ε-viniferin is able to reduce fat accumulation. Moreover, it prevents the development of some obesity co-morbidities, such as type 2 diabetes, dyslipidemias, hypertension and fatty liver. ε-viniferin can be absorbed orally, but it shows a very low bioavailability. In this scenario, further research on animal models is needed to confirm the effects reported in a great number of studies; to determine which metabolites are involved, including the main one responsible for the biological effects observed and the mechanisms that justify these effects. In a further phase, human studies should be addressed in order to use ε-viniferin as a new tool for obesity management, as a nutraceutical or to be included in functional foods.

Naringin Alleviates Glucose-Induced Aging by Reducing Fat Accumulation and Promoting Autophagy in Caenorhabditis elegans.

Naringin (Nar) is a dihydroflavonoid compound, widely found in citrus fruit and used in Chinese herbal medicine. As a phytochemical, it acts as a dietary supplement that can delay aging and prevent aging-related disease, such as obesity and diabetes. However, its exact mechanism remains unclear. In this study, the high-glucose-induced (HGI) Caenorhabditis elegans model was used to evaluate the anti-aging and anti-obesity effects of Nar. The mean lifespan and fast movement span of HGI worms were extended roughly 24% and 11%, respectively, by Nar treatment. Oil red O staining revealed a significant reduction in fat accumulation and dFP::LGG-labeled worms showed the promotion of autophagy. Additionally, whole transcriptome sequencing and gene set variation analysis suggested that Nar upregulated the lipid biosynthesis and metabolism pathways, as well as the TGF-β, Wnt and longevity signaling pathways. Protein-protein interaction (PPI) network analysis identified hub genes in these pathways for further analysis. Mutant worms and RNA interference were used to study mechanisms; the suppression of hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 disabled the fat-lowering, lifespan-prolonging, and health-promoting properties of Nar. Collectively, our findings indicate that Nar plays an important role in alleviating HGI-aging and anti-obesity effects by reducing fat accumulation and promoting autophagy.

Enhancement of Rabbit Meat Functionality by Replacing Traditional Feed Raw Materials with Alternative and More Sustainable Freshwater Cladophora glomerata Macroalgal Biomass in Their Diets.

Today's challenges in the animal husbandry sector, with customers' demand for more beneficial products, encourage the development of strategies that not only provide more sustainable production from the field to the table but also ensure final product functionality. Thus, the current research was aimed at replacing some traditional feed raw materials in rabbit diets with C. glomerata biomass to improve the functionality of meat. For this purpose, thirty weaned (52-d-old) Californian rabbits were assigned to 3 dietary treatments: standard compound diet (SCD), SCD + 4% C. glomerata (CG4), and SCD + 8% C. glomerata (CG8). At the end of the feeding trial, 122-d-old rabbits were slaughtered, longissimus dorsi (LD) and hind leg (HL) muscles were dissected post-mortem, and moisture, protein, and lipid profiles were determined. Results revealed that CG4 treatment can increase protein (22.17 g/kg), total (192.16 g/kg) and essential (threonine, valine, methionine, lysine, and isoleucine) amino acid levels in rabbit muscles. Both inclusions gradually reduced fat accumulation in muscles (CG8 < CG4 < SCD) but improved the lipid profile's nutritional value by decreasing saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) and increasing polyunsaturated fatty acids (PUFA). As the dose of C. glomerata increased, the level of lipid oxidation decreased. Biomass supplementation enhanced PUFA/SFA and h/H levels while decreasing thrombogenicity index (TI) and atherogenic index (AI) levels in rabbit muscles, potentially contributing to the prevention of heart disease. Overall, dietary supplementation with C. glomerata biomass may be a more beneficial and sustainable nutritional approach to functionally enhancing rabbit meat.

Effects of Monascus pigments on fat metabolism in Caenorhabditis elegans

Monascus spp. are traditional eatable filamentous fungi and have been utilized in China for more than one thousand years. Their fermented products, named hongqu, are a kind of traditional fermentation food and traditional Chinese medicine. Monascus pigments, the important polyketide secondary metabolites of Monascus have been widely used in food and medicine fields. It has been proved that Monascus pigments have a series of biological activities, such as anti-obesity activity, anticancer effects, antibacterial and antioxidant effects. The effects of Monascus pigments on nabolism and catabolism of lipid in Caenorhabditis elegans were studied. It was found that Monascus pigments could significantly reduce fat accumulation in the body of C. elegans wild-type (N2), reduce the contents of TG, MDA, CAT and ROS, and increase the content of SOD. At the same time, Monascus pigments can extend the maximum life span of nematodes and the tolerance time under emergency state, and Monascus pigments can reduce the accumulation of fat by improving the movement level of nematodes. The results of quantitative PCR showed that Monascus pigments inhibited the expression level of fat-5, fat-6, fat-7, mdt-15, pod-2, acs-2 and kat-1, and increased the expression level of nhr49, atgl-1 and ech-1 in wild-type (N2) C. elegans. Monascus pigments have the activity of reducing fat accumulation obviously, and can develop new functional products for its lipid-lowering characteristics and open up the market of functional food of monascus in our country.

Therapeutic Potential of Resveratrol and Atorvastatin Following High-Fat Diet Uptake-Induced Nonalcoholic Fatty Liver Disease by Targeting Genes Involved in Cholesterol Metabolism and miR33

The present study was designed to evaluate the effects of resveratrol, atorvastatin, and a combination of resveratrol and atorvastatin on expression levels of genes involved in the cholesterol metabolic pathway in the fatty liver of C57/BL6 mice. A high-fat diet was used to induce fatty liver in C57/BL6 mice treated with resveratrol, atorvastatin, or a combination of resveratrol and atorvastatin. Pathological and biochemical studies were performed. In addition, hepatic gene expressions of ATP-binding cassette transporter A1 (ABCA1), ABCG1, liver X receptor (LXR)α, scavenger receptor B1 (SR-B1), low-density lipoprotein receptor (LDLR), and miR33 were evaluated by the real-time PCR method, and the Western blot method was used to measure the ABCA1, ABCG1, and LXRα protein levels. Resveratrol and atorvastatin reduced fat accumulation in the liver of mice with fatty liver, and this effect was correlated with decreased blood glucose levels, triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol blood levels compared with the positive control (PC) group. In contrast to the animals of the PC group, fatty liver groups that received resveratrol and atorvastatin had a significant effect on the mRNA levels of the ABCA1, ABCG1, LXRα, SR-B1, LDLR, and miR33 genes. Moreover, resveratrol and atorvastatin administration elevated ABCA1 and ABCG1 and reduced LXRα protein expression. Obtained results showed that resveratrol and atorvastatin combination therapy can improve nonalcoholic fatty liver disease by targeting genes involved in cholesterol metabolism and miR33.

Catechins prevent obesity-induced kidney damage by modulating PPARγ/CD36 pathway and gut-kidney axis in rats

Obesity is an epidemic and a growing public health concern worldwide. It is one of the significant risk factors for developing chronic kidney disease. In the present study, we evaluated the preventive effect of green tea catechins (GTC) against obesity-induced kidney damage and revealed the underlying molecular mechanism of action. Various green tea catechins were quantified in the catechins-rich fraction using HPLC. In vitro, the palmitic and oleic acid-treated NRK-52E cells showed reduced fat accumulation and modulated expressions of PPARγ, CD36, and TGFβ after GTC treatment. In vivo, rats were fed with a high-fat diet (HFD), and the effect of GTC was assessed at 150 and 300 mg/kg body weight doses. HFD-fed rats showed a significant reduction in weight gain and improved serum creatinine, urea, and urine microalbumin levels after GTC treatment. The improved adipokines and insulin levels in GTC treated groups indicated the insulin-sensitizing effect. Histopathology revealed reduced degenerative changes, fibrous tissue deposition, and mesangial matrix proliferation in GTC treated groups. GTC treatment also downregulated the gene expressions of lipogenic and inflammatory factors and improved the altered expressions of CD36 and PPARγ in the kidney tissue. Further, GTC prevented gut dysbiosis in rats by promoting healthy microbes like Akkermansia muciniphila and Lactobacillus reuteri. Faecal metabolome revealed reduced saturated fatty acids, and improved amino acid levels in the GTC treated groups, which help to maintain gut health and metabolism. Overall, GTC prevented obesity-induced kidney damage by modulating PPARγ/CD36 signaling and maintaining gut health in rats.