Unexpected omega-3 activities in intracellular lipolysis and macrophage foaming revealed by fluorescence lifetime imaging.

Omega-3 polyunsaturated fatty acids (PUFA) found primarily in fish oil have been a popular supplement for cardiovascular health because they can substantially reduce circulating triglyceride levels in the bloodstream to prevent atherosclerosis. Beyond this established extracellular activity, here, we report a mode of action of PUFA, regulating intracellular triglyceride metabolism and lipid droplet (LD) dynamics. Real-time imaging of the subtle and highly dynamic changes of intracellular lipid metabolism was enabled by a fluorescence lifetime probe that addressed the limitations of intensity-based fluorescence quantifications. Surprisingly, we found that among omega-3 PUFA, only docosahexaenoic acid (DHA) promoted the lipolysis in LDs and reduced the overall fat content by approximately 50%, and consequently helped suppress macrophage differentiation into foam cells, one of the early steps responsible for atherosclerosis. Eicosapentaenoic acid, another omega-3 FA in fish oil, however, counteracted the beneficial effects of DHA on lipolysis promotion and cell foaming prevention. These in vitro findings warrant future validation in vivo.

Lipidomics analysis unveils the dynamic alterations of lipid degradation in rice bran during storage.

Recent explorations into rice bran oil (RBO) have highlighted its potential, owing to an advantageous fatty acid profile in the context of health and nutrition. Despite this, the susceptibility of rice bran lipids to oxidative degradation during storage remains a critical concern. This study focuses on the evolution of lipid degradation in RBO during storage, examining the increase in free fatty acids (FFAs), the formation of oxylipids, and the generation of volatile secondary oxidation products. Our findings reveal a substantial rise in FFA levels, from 109.55 to 354.06 mg/g, after 14 days of storage, highlighting significant lipid deterioration. Notably, key oxylipids, including 9,10-EpOME, 12,13(9,10)-DiHOME, and 13-oxoODE, were identified, with a demonstrated positive correlation between total oxylipids and free polyunsaturated fatty acids (PUFAs), specifically linoleic acid (LA) and α-linolenic acid (ALA). Furthermore, the study provides a detailed analysis of primary volatile secondary oxidation products. The insights gained from this study not only sheds light on the underlying mechanisms of lipid rancidity in rice bran but also offers significant implications for extending the shelf life and preserving the nutritional quality of RBO, aligning with the increasing global interest in this high-quality oil.

Lipidomics analysis of rice bran during storage unveils mechanisms behind dynamic changes in functional lipid molecular species.

Rice bran, recognized for its rich lipids and health-beneficial bioactive compounds, holds considerable promise in applications such as rice bran oil production. However, its susceptibility to lipid hydrolysis and oxidation during storage presents a significant challenge. In response, we conducted an in-depth metabolic profiling of rice bran over a storage period of 14 days. We focused on the identification of bioactive compounds and functional lipid species (25 acylglycerols and 53 phospholipids), closely tracking their dynamic changes over time. Our findings revealed significant reductions in these lipid molecular species, highlighting the impact of rancidity processes. Furthermore, we identified 19 characteristic lipid markers and elucidated that phospholipid and glycerolipid metabolism were key metabolic pathways involved. By shedding light on the mechanisms driving lipid degradation in stored rice bran, our study significantly advanced the understanding of lipid stability. These information provided valuable insights for countering rancidity and optimizing rice bran preservation strategies.

The molecular mechanism of obesity: The science behind natural exercise yoga and healthy diets in the treatment of obesity.

The review centers on the scientific evidence underlying obesity, providing a detailed examination of the role of perilipin in this condition. It explores potential causes of obesity and delves into therapeutic approaches involving exercise, yoga, and herbal treatments. The paper discusses natural sources that can contribute to combating obesity and underscores the importance of exercise in a scientific context for overcoming obesity. Additionally, it includes information on herbal ingredients that aid in reducing obesity. The review also examines the impact of exercise type and intensity at various time intervals on muscle development. It elucidates triglyceride hydrolysis through different enzymes and the deposition of fatty acids in adipose tissue. The mechanisms by which alpha/beta hydrolase domain-containing protein 5 (ABHD5) and hormone-sensitive lipase (HSL) target and activate their functions are detailed. The inflammatory response in obesity is explored, encompassing inflammatory markers, lipid storage diseases, and their classification with molecular mechanisms. Furthermore, the hormonal regulation of lipolysis is elaborated upon in the review.

Promote lipolysis in white adipocytes by magnetic hyperthermia therapy with Fe3O4microsphere-doped hydrogel.

Obesity has become an ongoing global crisis, since it increases the risks of cardiovascular disease, type 2 diabetes, fatty liver, cognitive decline, and some cancers. Adipose tissue is closely associated with the disorder of lipid metabolism. Several efforts have been made toward the modulation of lipid accumulation, but have been hindered by poor efficiency of cellular uptake, low safety, and uncertain effective dosage. Herein, we design an Fe3O4microsphere-doped composite hydrogel (Fe3O4microspheres @chitosan/ß-glycerophosphate/collagen), termed as Fe3O4@Gel, as the magnetocaloric agent for magnetic hyperthermia therapy (MHT), aiming to promote lipolysis in white adipocytes. The experimental results show that the obtained Fe3O4@Gel displays a series of advantages, such as fast sol-gel transition, high biocompatibility, and excellent magneto-thermal performance. MHT, which is realized by Fe3O4@Gel subjected to an alternating magnetic field, leads to reduced lipid accumulation, lower triglyceride content, and increased mitochondrial activity in white adipocytes. This work shows that Fe3O4@Gel-mediated MHT can effectively promote lipolysis in white adipocytesin vitro, which provides a potential approach to treat obesity and associated metabolic disorders.

Garcinia cambogia Extract Increased Hepatic Levels of Lipolysis-Stimulated Lipoprotein Receptor and Lipids in Mice on Normal Diet.

Garcinia cambogia extract (GCE) is a popular weight-loss supplement that also lowers plasma triglyceride (TG) levels. We hypothesized that GCE-mediated inhibition of ATP citrate lyase and thereby hepatic TG production could lead to compensatory mechanisms, including increased hepatic TG uptake via lipoprotein receptors. GCE (20 mg/day) administered 40 days orally to female C57BL/6Rj mice on a standard chow diet led to a decrease in both plasma fasting and post-prandial TG-rich lipoprotein levels, but with no significant change in body weight gain. Lipolysis stimulated lipoprotein receptor (LSR) protein levels, but not those of LDL-receptor, were increased as compared to controls. Mouse Hepa1-6 cells treated with the GCE active ingredient, hydroxycitrate, also led to increased LSR protein levels. Hepatic total cholesterol, TG, and muscle TG contents were higher in GCE-treated animals as compared to controls, whereas adipose TG levels were unchanged. LSR and LDL-receptor protein levels were correlated with liver total cholesterol, but only LDL-receptor was associated with liver TG. These results show that GCE treatment in mice on a standard chow diet led to significantly increased liver and muscle lipids, with no significant change in adipose tissue TG levels, which should be considered in the long-term use of GCE.

Placental extract suppresses lipid droplet accumulation by autophagy during the differentiation of adipose-derived mesenchymal stromal/stem cells into mature adipocytes.

OBJECTIVE: Placental extract, which contains various bioactive compounds, has been used as traditional medicine. Many studies have demonstrated additional applications of placental extract and provided a scientific basis for the broad spectrum of its effects. We have previously reported that porcine placental extract (PPE) strongly suppresses adipogenesis in a 3T3-L1 preadipocyte cell line, inhibiting differentiation. This study aimed to examine the effect of PPE on the accumulation of lipid droplets (LD) in adipose-derived mesenchymal stromal/stem cells (ASC). RESULTS: The study findings revealed that PPE decreased the size of LD during the differentiation of ASC into mature adipocytes. RT-qPCR analysis revealed that PPE increased the gene expression of lysosomal acid lipase A (Lipa), a lipolysis-related gene, in ASC-differentiated adipocytes. However, no differences were noted in the adipocyte differentiation markers (Pparg, Cebpa, and Adipoq), or the adipogenesis-related genes (Dgat1, Dgat2, Fasn, Soat1, and Soat2). In addition, PPE promoted autophagosome formation, which was partially co-localized with the LD, indicating that PPE accelerated the degradation of LD by inducing autophagy (termed lipophagy) during the differentiation of ASC into mature adipocytes. These results suggest that the use of PPE may be a potential novel treatment for regulating adipogenesis for the treatment of obesity.

Metabolic plasticity sustains the robustness of Caenorhabditis elegans embryogenesis.

Embryogenesis is highly dependent on maternally loaded materials, particularly those used for energy production. Different environmental conditions and genetic backgrounds shape embryogenesis. The robustness of embryogenesis in response to extrinsic and intrinsic changes remains incompletely understood. By analyzing the levels of two major nutrients, glycogen and neutral lipids, we discovered stage-dependent usage of these two nutrients along with mitochondrial morphology changes during Caenorhabditis elegans embryogenesis. ATGL, the rate-limiting lipase in cellular lipolysis, is expressed and required in the hypodermis to regulate mitochondrial function and support embryogenesis. The embryonic lethality of atgl-1 mutants can be suppressed by reducing sinh-1/age-1-akt signaling, likely through modulating glucose metabolism to maintain sustainable glucose consumption. The embryonic lethality of atgl-1(xd314) is also affected by parental nutrition. Parental glucose and oleic acid supplements promote glycogen storage in atgl-1(xd314) embryos to compensate for the impaired lipolysis. The rescue by parental vitamin B12 supplement is likely through enhancing mitochondrial function in atgl-1 mutants. These findings reveal that metabolic plasticity contributes to the robustness of C. elegans embryogenesis.

Anti-Adipogenic Activity of Rhaponticum carthamoides and Its Secondary Metabolites.

Besides their common use as an adaptogen, Rhaponticum carthamoides (Willd.) Iljin. rhizome and its root extract (RCE) are also reported to beneficially affect lipid metabolism. The main characteristic secondary metabolites of RCE are phytoecdysteroids. In order to determine an RCE's phytoecdysteroid profile, a novel, sensitive, and robust high-performance thin-layer chromatography (HPTLC) method was developed and validated. Moreover, a comparative analysis was conducted to investigate the effects of RCE and its secondary metabolites on adipogenesis and adipolysis. The evaluation of the anti-adipogenic and lipolytic effects was performed using human Simpson-Golabi-Behmel syndrome cells, where lipid staining and measurement of released glycerol and free fatty acids were employed. The HPTLC method confirmed the presence of 20-hydroxyecdysone (20E), ponasterone A (PA), and turkesterone (TU) in RCE. The observed results revealed that RCE, 20E, and TU significantly reduced lipid accumulation in human adipocytes, demonstrating their anti-adipogenic activity. Moreover, RCE and 20E were found to effectively stimulate basal lipolysis. However, no significant effects were observed with PA and TU applications. Based on our findings, RCE and 20E affect both lipogenesis and lipolysis, while TU only restrains adipogenesis. These results are fundamental for further investigations.

Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis.

INTRODUCTION: The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption. METHODS: We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase. RESULTS: The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase. CONCLUSION: The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.

Impact of Grape Seed Powder and Black Tea Brew on Lipid Digestion-An In Vitro Co-Digestion Study with Real Foods.

Effects of two foods with bioactive constituents (black tea brew, BTB and grape seed powder, GSP) on lipid digestibility was studied. Lipolysis inhibitory effect of these foods was examined using two test foods (cream and baked beef) with highly different fatty acid (FA) composition. Digestion simulations were performed either using both gastric and pancreatic lipase, or only with pancreatic lipase according to the Infogest protocol. Lipid digestibility was assessed based on the bioaccessible FAs. Results showed the triacylglycerols containing short- and medium-chain FAs (SCFA and MCFA) are non-preferred substrates for pancreatic lipase; however, this is not characteristic for GL. Our findings suggest that both GSP and BTB primarily affect the lipolysis of SCFAs and MCFAs, because the dispreference of pancreatic lipase towards these substrates was further enhanced as a result of co-digestion. Interestingly, GSP and BTB similarly resulted in significant decrease in lipolysis for cream (containing milk fat having a diverse FA profile), whereas they were ineffective in influencing the digestion of beef fat, having simpler FA profile. It highlights that the characteristics of the dietary fat source of a meal can be a key determinant on the observed extent of lipolysis when co-digested with foods with bioactive constituents.

An Artemisia scoparia extract attenuates glucocorticoid-induced lipolysis in adipocytes.

OBJECTIVE: Prescription glucocorticoid (GC) use is widespread across developed countries for the treatment of several inflammatory conditions. Elevated GCs are known to promote lipolysis and metabolic disorders. An extract of Artemisia scoparia (SCO) has been shown to reduce lipolysis and promote metabolic health but has not been investigated in the context of excess GCs. Our aim was to examine the effects of SCO on GC-induced lipolysis. METHODS: Mature adipocytes were pretreated with vehicle or SCO, then exposed to either the synthetic GC dexamethasone (DEX) or tumor necrosis factor alpha (TNFα). Medium was collected and assayed for glycerol and fatty acids as measures of lipolysis. The expression of several lipolytic genes and proteins was assessed, and the involvement of glucocorticoid receptor (GR) in SCO's effects was also interrogated. RESULTS: SCO significantly attenuated DEX-induced lipolysis but did not interfere with DEX-mediated changes in inflammatory gene profiles in adipocytes. SCO treatment resulted in significant reductions in monomeric phosphodiesterase (PDE) protein levels while elevating PDE multimeric complex formation, but other canonical lipolytic mediators were unaltered. SCO attenuated lipolysis even when GR expression was significantly knocked down. Finally, it was demonstrated that SCO was distinct from rosiglitazone in its antilipolytic effects. CONCLUSIONS: SCO attenuates GC-induced lipolysis independently of GR activity. Future studies are needed to elucidate underlying mechanisms.

Impact of process and composition of formulas for elderly on in vitro digestion using the dynamic DIDGI® model.

Due to the lower efficiency of the elderly digestion system, new formulations are needed in order to increase the bioaccessibility of macronutrients. The aim of the work was to evaluate the effect of the process of protein sources production using either liquid (F2) vs spray dried milk proteins (F1/F3) and the source of lipids (vegetable oil (F1) vs mix of vegetable oil + bovine milk cream (F2/F3)) ingredients on the macronutrient digestion of three experimental elderly formulas. The dynamic in vitro digestion model DIDGI®, was adapted to simulate the digestive conditions of the elderly. An exhaustive review of the literature was carried out in order to simulate as closely as possible the elderly digestive parameters and constituted the starting point towards a consensus in vitro digestion model that will be proposed soon by the INFOGEST scientific network. The three experimental formulas (F1/F2/F3) differing by the composition and process applied were submitted to the DIDGI® dynamic in vitro digestion over four hours using parameters adapted to the elderly. The three formulas were compared in terms of proteolysis and lipolysis. A slight impact of the process (liquid vs spray-dried) on the degree of proteolysis at the end of digestion was observed with 50.8% for F2 compared to 56.8% for F1 and 52.9% for F3 with<5% of difference between the 3 formulas. Concerning the degree of lipolysis, the addition of bovine cream led to a lesser extent of lipolysis with 63.7 and 60.2% for F2 and F3 respectively versus 66.3% for F1 (containing only vegetable oil). Our results highlighted the beneficial input of the milk fat with a higher level of phospholipids and a lower ω6/ω3 PUFA ratio and can be a good alternative to the use of the vegetable fat in drinks for elderly people.

Diet Supplementation of Luteolin before Fatty Liver Formation Improves Hepatic Steatosis in Obese Mice by Inhibiting Visceral Adipose Tissue Lipolysis.

SCOPE: Serotonin (5-HT)-induced visceral adipocyte lipolysis is essential for the development of obesity-related complications. Diet supplementation of luteolin prevents high-fat diet (HFD)-fed mice against obesity and associated fatty liver. However, independent of the body weight loss, whether dietary luteolin can substantially reduce hepatic steatosis remains unclear. METHODS AND RESULTS: In differentiated 3T3-L1 cells, 5-HT treatment promotes adipocyte lipolysis, while luteolin significantly inhibits 5-HT-induced lipolysis, Ca2+ -PKG cascade, and SIRT1/FoxO1/AMPKα signaling through binding to 5-HT receptor HTR2B. Further, 5-week-old mice are fed with an HFD for 16 weeks. At the 6th, 8th, or 10th weeks of HFD feeding, some mice are switched to a luteolin-containing HFD, respectively. In all HFD-fed mice, body weight gain and body component are unaffected by dietary luteolin. However, diet supplementation of luteolin at the 6th or 8th, rather than at the 10th weeks, alleviates hepatic steatosis. Meanwhile, dietary luteolin reduces epididymal adipose tissue (EAT) lipolysis, and represses the level of lipolytic enzyme, the expression of Htr2b, and the activation of PKG and SIRT1/FoxO1/AMPKα signaling in EAT. CONCLUSIONS: Diet supplementation of luteolin before the formation of fatty liver protects HFD-fed mice against ectopic lipid deposition in liver by inhibiting visceral adipocyte lipolysis.

Curcumin treatment suppresses cachexia-associated adipose wasting in mice by blocking the cAMP/PKA/CREB signaling pathway.

BACKGROUND: Cachexia is a multifactorial debilitating syndrome that is responsible for 22% of mortality among cancer patients, and there are no effective therapeutic agents available. Curcumin, a polyphenolic compound derived from the plant turmeric, has been shown to have anti-inflammatory, antioxidant, anti-autophagic, and antitumor activities. However, its function in cancer cachexia remains largely unexplored. PURPOSE: This study aimed to elucidate the mechanisms by which curcumin improves adipose atrophy in cancer cachexia. METHODS: C26 tumor-bearing BALB/c mice and ß3-adrenoceptor agonist CL316243 stimulated BALB/c mice were used to observe the therapeutic effects of curcumin on the lipid degradation of cancer cachexia in vivo. The effects of curcumin in vitro were examined using mature 3T3-L1 adipocytes treated with a conditioned medium of C26 tumor cells or CL316243. RESULTS: Mice with C26 tumors and cachexia were protected from weight loss and adipose atrophy by curcumin (50 mg/kg, i.g.). Curcumin significantly reduced serum levels of free fatty acids and increased triglyceride levels. In addition, curcumin significantly inhibited PKA and CREB activation in the adipose tissue of cancer cachectic mice. Curcumin also ameliorated CL316243-induced adipose atrophy and inhibited hormone-mediated PKA and CREB activation in mice. Moreover, the lipid droplet degradation induced by C26 tumor cell conditioned medium in mature 3T3-L1 adipocytes was ameliorated by curcumin (20 µM) treatment. Curcumin also improved the lipid droplet degradation of mature 3T3-L1 adipocytes induced by CL316243. CONCLUSION: Curcumin might be expected to be a therapeutic supplement for cancer cachexia patients, primarily through inhibiting adipose tissue loss via the cAMP/PKA/CREB signaling pathway.

Si-Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS) is a famous Chinese herbal formula used in China for thousands of years. It has clinical effects on a variety of lipid metabolism disorders, but the ameliorating effects of SNS on obesity and underlying mechanisms remained poorly elucidated. AIM OF THE STUDY: This study aims to explore the therapeutic effect and mechanism of SNS on obesity from multiple perspectives in vitro and in vivo. MATERIALS AND METHODS: The high-fat diet (HFD)-induced obesity mouse model was established to evaluate the effect of SNS. Then network pharmacologic methods were performed to predict underlying mechanisms, and the core pathways were verified in animal and cell studies. RESULTS: Our results demonstrated that SNS significantly reduced body weight, body fat content, white adipose tissue (WAT) expansion in obese mice, and lipid accumulation in primary mouse embryonic fibroblasts (MEFs) cells. Network pharmacologic analysis identified 66 potential therapeutic targets, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these genes revealed that the most important signaling pathway includes AMP-activated protein kinase (AMPK) signaling pathway, regulation of lipolysis in adipocytes, lipid and atherosclerosis. Western blot assay confirmed that SNS activated hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) activity and promoted lipolysis through AMPK signaling pathway. CONCLUSION: The results confirmed that SNS improves lipid accumulation through AKT/AMPK/HSL axis mediated lipolysis, which opens a new option for clinical treatment of obesity and associated complications.

Soy lecithin increases the stability and lipolysis of encapsulated algal oil and probiotics complex coacervates.

BACKGROUND: Co-encapsulation of probiotics and omega-3 oil using complex coacervation is an effective method for enhancing the tolerance of probiotics under adverse conditions, whereas complex coacervation of omega-3 oil was found to have low lipid digestibility. In the present study, gelatin (GE, 30 g kg-1 ) and gum arabic (GA, 30 g kg-1 ) were used to encapsulate Lactobacillus plantarum WCFS1 and algal oil by complex coacervation to produce microcapsules containing probiotics (GE-P-GA) and co-microcapsules containing probiotics and algal oil (GE-P-O-GA), and soy lecithin (SL) was added to probiotics-algal oil complex coacervates [GE-P-O(SL)-GA] to enhance its stability and lipolysis. Then, we evaluated the viability of different microencapsulated probiotics exposed to freeze-drying and long-term storage, as well as the survival rate and release performance of encapsulated probiotics and algal oil during in vitro digestion. RESULTS: GE-P-O(SL)-GA had a smaller particle size (51.20 µm), as well as higher freeze-drying survival (90.06%) of probiotics and encapsulation efficiency of algal oil (75.74%). Moreover, GE-P-O(SL)-GA showed a higher algal oil release rate (79.54%), lipolysis degree (74.63%) and docosahexaenoic acid lipolysis efficiency (64.8%) in the in vitro digestion model. The viability of microencapsulated probiotics after simulated digestion and long-term storage at -18,4 and 25 °C was in the order: GE-P-O(SL)-GA > GE-P-O-GA > GE-P-GA. CONCLUSION: As a result of its amphiphilic properties, SL strongly affected the physicochemical properties of probiotics and algal oil complex coacervates, resulting in higher stability and more effective lipolysis. Thus, the GE-P-O(SL)-GA can more effectively deliver probiotics and docosahexaenoic acid to the intestine, which provides a reference for the preparation of high-viability and high-lipolysis probiotics-algal oil microcapsules. © 2022 Society of Chemical Industry.

Naringin reduces fat deposition by promoting the expression of lipolysis and ß-oxidation related genes.

AIMS: Naringin, a flavonoid present in citrus fruits, has been known for the capacity to reduce lipid synthesis and anti-inflammatory. In this study, we investigated whether naringin increases lipolysis and fatty acid ß-oxidation to change fat deposition. METHODS: In in vivo experiment, obese adult mice (20-weeks-old, n = 18) were divided into control group fed with normal diet and naringin-treated group fed with naringin-supplemented diet (5 g/kg) for 60 days, respectively. In in vitro experiment, differentiated 3T3-L1 adipocytes were treated for four days with or without naringin (100 µg/mL). RESULTS: Supplementing naringin significantly reduced the body weight, abdominal fat weight, blood total cholesterol content of mice, but did not affect food intake. In addition, naringin decreased levels of pro-inflammatory factors in adipose tissue including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and monocyte chemotactic protein 1 (MCP-1). Naringin increased the expression of AMP-activated protein kinase (AMPK), a key factor in cellular energy metabolism, and raised the ratio of p-AMPK/AMPK in mouse liver tissue. The protein expression of hormone-sensitive lipase (HSL), phospho-HSL563 (p-HSL563), p-HSL563/HSL, and adipocyte triglyceride lipase (ATGL) was significantly increased in the adipose tissue of naringin-treated mice. Furthermore, naringin enhanced the expression of fatty acid ß-oxidation genes, including carnitine palmitoyl transferase 1 (CPT1), uncoupling protein 2 (UCP2), and acyl-coenzyme A oxidase 1 (AOX1) in mouse adipose tissue. In in vitro experiment, similar findings were observed in differentiated 3T3-L1 adipocytes with naringin treatment. The treatment remarkably reduced intracellular lipid content, increased the number of mitochondria and promoted the gene expression of HSL, ATGL, CPT1, AOX1, and UCP2 and the phosphorylation of HSL protein. CONCLUSION: Naringin reduced body fat in obese mice and lipid content in differentiated 3T3-L1 adipocytes, which was associated with enhanced AMPK activation and upregulation of the expression of the lipolytic genes HSL, ATGL, and ß-oxidation genes CPT1, AOX1, and UCP2.

Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity.

The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. O-linked ß-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation.

Amycenone reduces excess body weight and attenuates hyperlipidaemia by inhibiting lipogenesis and promoting lipolysis and fatty acid ß-oxidation in KK-Ay obese diabetic mice.

Excess body weight and hyperlipidaemia cause severe health problems and have social implications. Amycenone is an active substance extracted from Yamabushitake mushrooms with no reports of its activity against excess body weight and hyperlipidaemia. This research clarifies the effects and mechanisms of action of amycenone on the inhibition of body weight excess and hyperlipidaemia attenuation using KK-Ay mice. Amycenone or water was administered to 8-week-old male KK-Ay mice by gavage for 8 weeks. Their body weight and food intake were recorded during the experiment. At the end of the experimental period, the mice were dissected, and blood samples, lipid metabolism-related organs and tissues were collected and stored for further analysis. Amycenone treatment suppressed body weight gain and improved serum levels of fasting blood glucose and non-esterified fatty acids. Additionally, serum and hepatic cholesterol and triacylglycerol levels were reduced after this treatment, whereas the phosphorylation levels of AMPK, PKA and HSL increased and the expression level of FAS decreased. The protein level of C/EBPß and gene expression level of Cpt1 were higher in the perirenal adipose tissue of amycenone-treated KK-Ay mice. Furthermore, amycenone phosphorylated AMPK, PKA and ACC, and PPARγ expression was lower in the mesenteric adipose tissue. The phosphorylation levels of AMPK, LKB1, PKA and ACC were also induced, and FAS expression level was reduced in the liver of the amycenone-treated group. Amycenone could reduce excess body weight and attenuate hyperlipidaemia in KK-Ay mice by inhibiting lipogenesis and promoting lipolysis through lipid metabolism pathway stimulation and fatty acid ß-oxidation acceleration.