Fat Accumulation In Adipose Tissue Research Articles

Lysine 2-hydroxyisobutyrylation levels determined adipogenesis and fat accumulation in adipose tissue in pigs

BackgroundExcessive backfat deposition lowering carcass grade is a major concern in the pig industry, especially in most breeds of obese type pigs. The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear. Lysine 2-hydroxyisobutyrylation (Khib), is a novel protein post-translational modification (PTM), which play an important role in transcription, energy metabolism and metastasis of cancer cells, but its role in adipogenesis and fat accumulation has not been shown.ResultsIn this study, we first analyzed the modification levels of acetylation (Kac), Khib, crotonylation (Kcr) and succinylation (Ksu) of fibro-adipogenic progenitors (FAPs), myogenic precursors (Myo) and mesenchymal stem cells (MSCs) with varied differentiation potential, and found that only Khib modification in FAPs was significantly higher than that in MSCs. Consistently, in parallel with its regulatory enzymes lysine acetyltransferase 5 (KAT5) and histone deacetylase 2 (HDAC2) protein levels, the Khib levels increased quadratically (P < 0.01) during adipogenic differentiation of FAPs. KAT5 knockdown in FAPs inhibited adipogenic differentiation, while HDAC2 knockdown enhanced adipogenic differentiation. We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs (Laiwu pigs) and lean-type pigs (Duroc pigs), respectively. Accordingly, the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese- and lean-type pigs.ConclusionsFrom the perspective of protein translational modification, we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs, and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.

Relationship Between Physical Activity and Junk Food Consumption on the Incidence of Early Menarche

Puberty is a period of change between childhood and adolescence towards adulthood. Early puberty or also called precocious puberty is when girls have signs of puberty before the age of 11 years. The incidence of early menarche in adolescents is increasing in Indonesia. Early menarche increases the risk of cancer such as breast cancer, abdominal obesity, fat accumulation in adipose tissue, cardovascular disease, hypertension and premarital pregnancy. In adolescence, lifestyles and habits change, and one of them is trying new foods. This study identifies whether there is an association between fast food factors and adolescent activity with the occurrence of early menarche. The results of the study on 40 elementary school students in Cikarang female students who did not have early menarche were 20 (50.0%) and female students who had early menarche were 20 (50.0%). In an unhealthy lifestyle and early menarche as many as 14 or 70.0% of students. As for the physical activity of sports schoolgirls with the category of light exercise and early menarche as many as 7 or 35.0%. in students often consume Fast Food and early menarche as many as 15 or 75.0%.

The effect of intermittent fasting 5:2 on IL-6 levels in obese male employees in Jakarta

Background: Obesity is a condition of excessive fat accumulation in adipose tissue. This condition causes endothelial damage, increase macrophage infiltration, and inflammation in adipose tissue. Inflammation happens due to the increase of interleukin-6 (IL-6) as a proinflammatory cytokine which responsible for the occurrence of chronic diseases. Intermittent fasting is a potentially effective method for losing weight and suggested can reduce levels of proinflammatory cytokines.&#x0D; Objective: The aim of this study is to determine the effect of 5:2 intermittent fasting on IL-6 cytokine levels in obese employees in Jakarta.&#x0D; Methods: This study used a cross-sectional method conducted on 50 healthy male employees aged 19–52 years with a body mass index (BMI) ≥25 kg/m2. Subjects were divided into two groups, the 5:2 intermittent fasting group and the non-fasting group. Intermittent fasting 5:2 was observed every Monday and Thursday for eight weeks. IL-6 levels were obtained through examination using an enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis was performed by Mann Whitney and Kruskal Wallis test.&#x0D; Results: The results showed that the median of IL-6 levels decreased in fasting group from 5,10 (1.06–9.81) pg/mL to 4.64 (1.00–13.39) pg/mL and increased in non-fasting group from 3.65 (1.17–38.70) pg /mL to 6.35 (2.44–19.86) pg/mL, but the change was not significant.&#x0D; Conclusion: Intermittent fasting 5:2 tend to decrease IL-6 levels in obese male employees in Jakarta although the change of IL-6 level was not significant.

Effect of Dangke consumption on body weight, blood glucose, and total cholesterol in rats subjected to high-fat and fructose diet

Obesity occurs due to an imbalance in caloric intake, leading to excess fat accumulation in adipose tissue. This condition is associated with hyperglycemia and abnormal lipid levels. Dangke, a traditional Indonesian cheese, contains lactic acid bacteria and bioactive peptides known for their health benefits. This study aims to assess the effects of dangke consumption on body weight, glucose, and total cholesterol levels in rats subjected to a high-fat and fructose diet (HFFD). This research employed an experimental laboratory design. Twenty-four Sprague-Dawley rats, with weights ranging from 100 to 200 g, were divided into six groups, each consisting of four rats. Group 1 (ND) (received a normal diet. Group 2 (HFFD) was provided with a high-fat and fructose diet).

Brassica rapa L. prevents Western diet-induced obesity in C57BL/6 mice through its binding capacity of cholesterol and fat.

Obesity, a chronic disorder caused by excessive energy intake leading to fat accumulation in adipose tissue, increases the risk of severe diseases. Brassica rapa L. is known as a traditional vegetable in the Nagano area of Japan. C57BL/6 mice were randomly assigned to three groups, with different diets as follows: a normal diet, a Western diet (WD), and a WD plus B. rapa L. powder (BP) in a 56-day experiment. Brassica rapa L. supplementation reduced the body weight gain and lipid accumulation of mice significantly. The BP group also had higher fecal bile acid, total cholesterol, and triglyceride excretion levels compared with those in the other groups. The antiobesity effects of B. rapa L. were due to its binding with cholesterol and fat, and possibly enhancing the bile acid excretion and modulating gut microbiota, suggesting thatB. rapaL. could be a functional vegetable with potential uses in targeting obesity.

High fat in blood and body and increased risk of clinically diagnosed non-alcoholic fatty liver disease in 105,981 individuals

Background and aimsHigh caloric diets rich in fat and carbohydrates lead to increased fat accumulation in adipose tissue and blood. This may lead to increased risk of non-alcoholic fatty liver disease. We hypothesized that baseline high nonfasting plasma triglycerides, body mass index (BMI), and waist circumference, individually and combined, associate with increased risk of clinically diagnosed non-alcoholic fatty liver disease during follow-up. MethodsCohort of 105,981 white Danish individuals recruited in 2003–2015 with end of follow-up on December 13th, 2018. Mean follow-up was 9.2 years during which time 418 were clinically diagnosed at hospitals with non-alcoholic fatty liver disease. ResultsRisk of clinically diagnosed non-alcoholic fatty liver disease increased with higher plasma triglycerides, higher BMI, and with higher waist circumference, continuously and stepwise using multivariable adjusted hazard ratios and cumulative incidences. Combining clinical categories of plasma triglycerides with BMI or waist circumference categories, illustrated an almost additive risk with increasing categories. Compared with plasma triglycerides of <1 mmol/L and BMI <25 kg/m2, the multivariable adjusted hazard ratio was 5.2(95% confidence interval: 1.3–21.6) for individuals with both plasma triglycerides of ≥5 mmol/L and BMI ≥35 kg/m2. The corresponding hazard ratio for individuals with plasma triglycerides ≥5 mmol/L and waist circumference was >88 cm for women and >102 cm for men was 4.8(2.3–9.7). Triglyceride results were more pronounced in women versus men. ConclusionsHigh fat in blood and body measured by plasma triglycerides, BMI, and waist circumference, individually and especially combined, are associated with up to a 5-fold increased risk of clinically diagnosed non-alcoholic fatty liver disease.

A Study on Body Fat Percentage for Physical Fitness and Prevention of Obesity: A Two Compartment Model

The minimal amount of body fat is necessary for normal physiological functions that manages body temperature, creates energy to perform all the physical activities, and protects the organs of human body. Storage body fat consists of fat accumulation in adipose tissue. Total body fat in human body is the sum of essential fat and storage fat. At present body fat percentage is considered as one of the most accurate obesity evaluation tools. To determine body fat accurately the clinicians should use the most appropriate, accurate, and accessible strategies available in the scientific research area. Accurate measurement of body fat and lean body is essential for the nutrition assessment, and an individual’s overall health and well-being. In this study some measurement processes are discussed to determine body fat percentage (BFP) properly of a person by the analysis of two compartment model: fat mass and fat free mass.

Proteomic Analysis of Skeletal Muscle and White Adipose Tissue after Aerobic Exercise Training in High Fat Diet Induced Obese Mice

Obesity is associated with excessive fat accumulation in adipose tissue and other organs, such as skeletal muscle, whereas aerobic exercise (AE) plays an important role in managing obesity through profound protein regulation. Our study aimed to investigate the impact of AE on proteomic changes in both the skeletal muscle and the epididymal fat pad (EFP) of high-fat-diet-induced obese mice. Bioinformatic analyses were performed on differentially regulated proteins using gene ontology enrichment analysis and ingenuity pathway analysis. Eight weeks of AE significantly reduced body weight, increased the serum FNDC5 level, and improved the homeostatic model assessment of insulin resistance. A high-fat diet caused alterations in a subset of proteins involved in the sirtuin signaling pathway and the production of reactive oxygen species in both skeletal muscle and EFP, leading to insulin resistance, mitochondrial dysfunction, and inflammation. On the other hand, AE upregulated skeletal muscle proteins (NDUFB5, NDUFS2, NDUFS7, ETFD, FRDA, and MKNK1) that enhance mitochondrial function and insulin sensitivity. Additionally, the upregulation of LDHC and PRKACA and the downregulation of CTBP1 in EFP can promote the browning of white adipose tissue with the involvement of FNDC5/irisin in the canonical pathway. Our study provides insights into AE-induced molecular responses and may help further develop exercise-mimicking therapeutic targets.

The Perspectives of Plant Natural Products for Mitigation of Obesity

Obesity is a metabolic disease caused by an imbalance between energy intake and consumption, which leads to excessive fat accumulation in adipose tissues [...].

Preventive Effect of Indian Gooseberry (Phyllanthus emblica L.) Fruit Extract on Cognitive Decline in High-Fat Diet (HFD)-Fed Rats.

Methylglyoxal (MG)-derived advanced glycation end products (AGEs) directly bind to the receptor for advanced glycation end products (RAGE), subsequently exacerbating obesity and obesity-induced cognitive decline. Indian gooseberry (Phyllanthus emblica L.) fruit has antiobesity properties. However, the underlying mechanism by which Indian gooseberry fruit prevents obesity-induced cognitive decline remains unclear. This study aims to investigate the preventive effect of a water extract of Indian gooseberry fruit (WEIG) and its bioactive compound gallic acid (GA) on the obesity-induced cognitive decline through MG suppression and gut microbiota modulation in high-fat diet (HFD)-fed rats. Trapping MG, WEIG, and GA significantly ameliorate fat accumulation in adipose tissue and learning and memory deficits. Mechanistically, WEIG and GA administration effectively reduces brain MG and AGE levels and subsequently reduces insulin resistance, inflammatory cytokines, MDA production, and Alzheimer's disease-related proteins, but increases both antioxidant enzyme activities and anti-inflammatory cytokine with inhibiting RAGE, MAPK, and NF-κB levels in HFD-fed rats. Additionally, WEIG and GA supplementation increases the relative abundances of Bacteroidetes, Gammaproteobacteria, and Parasutterella, which negatively correlate with MG, inflammatory cytokine, and Alzheimer's disease-related protein expressions. This novel finding provides a possible mechanism by which WEIG prevents obesity-induced cognitive decline through the gut-brain axis.

KLF regulation of insulin pathway genes.

Alteration in lipid metabolism can result in fat accumulation in adipose tissues, which may lead to two most important human diseases, obesity and diabetes. A shift in lipid metabolism deregulates signaling pathways which regulates obesity and/or diabetes. In this study, we examined the components of insulin/ TGF-β pathways and their genetic interaction with Krüppel-like transcription factors (KLFs). Their role in energy homeostasis were discussed. We separately created klf/daf genes double mutants by carrying out klfs RNAi on daf-2 (e1391), daf-4 (e1364), daf-7 (e1372); dpy-1 (e1), daf-14 (m77), daf-16 (mgDf50) mutants. And then conducted Oil O Red staining to assay the klf/daf RNAi worms for fat deposits and examine genetic interaction between klfs and daf genes. The results showed that worms bearing klf-1, 2, or 3 and daf-2, or daf-4 mutations deposit large, but similar fat levels as individual mutants. The results suggested that they target the same molecular pathway of fat storage. klf-1, 2 or 3 RNAi /daf-7 worms showed higher fat deposits in klf-1, 2, or 3 RNAi/daf-7 worms than klf-1, 2, or 3 RNAi or daf-7 mutants alone, which showed a functional interaction between klfs and daf-7 in perhaps TGF-β-like pathway. Altogether our study suggests a direct role of klfs in insulin signaling pathway.

Partial MCT1 invalidation protects against diet-induced non-alcoholic fatty liver disease and the associated brain dysfunction.

Non-alcoholic fatty liver disease (NAFLD) has been associated with mild cerebral dysfunction and cognitive decline, although the exact pathophysiological mechanism remains ambiguous. Using a diet-induced model of NAFLD and monocarboxylate transporter-1 (Mct1+/-) haploinsufficient mice, which resist high-fat diet-induced hepatic steatosis, we investigated the hypothesis that NAFLD leads to an encephalopathy by altering cognition, behaviour, and cerebral physiology. We also proposed that global MCT1 downregulation offers cerebral protection. Behavioural tests were performed in mice following 16 weeks of control diet (normal chow) or high-fat diet with high fructose/glucose in water. Tissue oxygenation, cerebrovascular reactivity, and cerebral blood volume were monitored under anaesthesia by multispectral optoacoustic tomography and optical fluorescence. Cortical mitochondrial oxygen consumption and respiratory capacities were measured using exvivo high-resolution respirometry. Microglial and astrocytic changes were evaluated by immunofluorescence and 3D reconstructions. Body composition was assessed using EchoMRI, and liver steatosis was confirmed by histology. NAFLD concomitant with obesity is associated with anxiety- and depression-related behaviour. Low-grade brain tissue hypoxia was observed, likely attributed to the low-grade brain inflammation and decreased cerebral blood volume. It is also accompanied by microglial and astrocytic morphological and metabolic alterations (higher oxygen consumption), suggesting the early stages of an obesogenic diet-induced encephalopathy. Mct1 haploinsufficient mice, despite fat accumulation in adipose tissue, were protected from NAFLD and associated cerebral alterations. This study provides evidence of compromised brain health in obesity and NAFLD, emphasising the importance of the liver-brain axis. The protective effect of Mct1 haploinsufficiency points to this protein as a novel therapeutic target for preventing and/or treating NAFLD and the associated brain dysfunction. This study is focused on unravelling the pathophysiological mechanism by which cerebral dysfunction and cognitive decline occurs during NAFLD and exploring the potential of monocarboxylate transporter-1 (MCT1) as a novel preventive or therapeutic target. Our findings point to NAFLD as a serious health risk and its adverse impact on the brain as a potential global health system and economic burden. These results highlight the utility of Mct1 transgenic mice as a model for NAFLD and associated brain dysfunction and call for systematic screening by physicians for early signs of psychological symptoms, and an awareness by individuals at risk of these potential neurological effects. This study is expected to bring attention to the need for early diagnosis and treatment of NAFLD, while having a direct impact on policies worldwide regarding the health risk associated with NAFLD, and its prevention and treatment.

Protective effect of rosmarinic acid-rich extract from Trichodesma khasianum Clarke against microbiota dysbiosis in high-fat diet-fed obese mice

Hypertrophy of adipose tissues and dysbiosis are hallmarks of obesity. Although drugs are applied for obesity treatment, side effects limit their use. The anti-obesity capacity of rosmarinic acid (RA) has been documented. Trichodesma khasianum Clarke is an edible RA-rich plant grown in Taiwan. Our previous study found that an 80 % ethanol extract of T. khasianum Clarke leaves (80EETC) ameliorates gastric mucosal damage through its anti-inflammatory, antioxidant, and microbiota modulation abilities. However, the anti-obesity effect of 80EETC remains unclear. Therefore, the objective of this study was to explore the protective effects of low-dose 80EETC (125 mg/kg b.w., 80EETCL) or high-dose 80EETC (250 mg/kg b.w., 80EETCH) on obesity development through gut microbiota modulation in high-fat diet (HFD)-induced C57BL/6 mice. The results showed a high RA content (89.2 ± 7.4 mg/g) in 80EETC. 80EETC administration significantly decreased body weight, body fat ratio, serum lipid levels (TC, TG, and LDL-C), adipose tissue accumulation, malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) in HFD-fed mice. Furthermore, supplementation with 80EETC reduced the Firmicutes/Bacteroidetes ratio and enhanced the relative abundance of gut microbiota (p_Bacteroidetes, f_Lactobacillus, f_Muribaculaceae, f_Prevotellaceae, g_Lactobacillus, g_Prevotellaceae_NK3B31_group, g_Ruminococcaceae_UCG–013, and g_Ruminococcaceae_UCG–014), which negatively correlated with obesity-related factors such as body weight, energy intake, fat accumulation in adipose tissue, TC, TG, LDL, and MDA. In conclusion, RA-rich 80EETC had a protective effect against obesity development and it has potential in healthy food applications.

From the Editor’s Desk…

From the Editor’s Desk…

Neurosecretory Protein GL Promotes Normotopic Fat Accumulation in Male ICR Mice.

Neurosecretory protein GL (NPGL) is a small secretory protein identified in the hypothalamus of birds and mammals. We recently reported that NPGL exerts obesogenic effects in obesity-prone C57BL6/J mice. However, whether NPGL elicits adiposity in different mouse strains is poorly understood. In this study, we generated transgenic mice overexpressing Npgl using the ICR strain (Npgl Tg mice) to elucidate the obesogenic effects of NPGL in different strains. Npgl Tg mice showed increased white adipose tissue (WAT) mass. Although the mass of brown adipose tissue (BAT) was slightly altered in Npgl Tg mice, hypertrophy of lipid droplets was also observed in BAT. In contrast, fat accumulation was not induced in the liver, with the upregulation of mRNAs related to hepatic lipolysis. These results support the hypothesis that NPGL causes obesity in several strains and species. This report highlights the pivotal role of NPGL in fat accumulation in adipose tissues and contributes to the elucidation of the biological mechanisms underlying obesity and metabolic diseases in heterogeneous populations.

The energy balance model of obesity: beyond calories in, calories out

A recent Perspective article described the "carbohydrate-insulin model (CIM)" of obesity, asserting that it "better reflects knowledge on the biology of weight control" as compared with what was described as the "dominant energy balance model (EBM)," which fails to consider "biological mechanisms that promote weight gain." Unfortunately, the Perspective conflated and confused the principle of energy balance, a law of physics that is agnostic as to obesity mechanisms, with the EBM as a theoretical model of obesity that is firmly based on biology. In doing so, the authors presented a false choice between the CIM and a caricature of the EBM that does not reflect modern obesity science. Here, we present a more accurate description of the EBM where the brain is the primary organ responsible for body weight regulation operating mainly below our conscious awareness via complex endocrine, metabolic, and nervous system signals to control food intake in response to the body's dynamic energy needs as well as environmental influences. We also describe the recent history of the CIM and show how the latest "most comprehensive formulation" abandons a formerly central feature that required fat accumulation in adipose tissue to be the primary driver of positive energy balance. As such, the new CIM can be considered a special case of the more comprehensive EBM but with a narrower focus on diets high in glycemic load as the primary factor responsible for common obesity. We review data from a wide variety of studies that address the validity of each model and demonstrate that the EBM is a more robust theory of obesity than the CIM.

Research Progress of Ferroptosis in Adiposity-Based Chronic Disease (ABCD).

Ferroptosis is a multistep regulated cell death process induced by iron accumulation and lipid peroxidation. Classical GPX4-dependent pathway and GPX4-independent pathways can independently and synergistically inhibit ferroptosis and jointly maintain the oxidative balance of the body. WHO defines obesity as “a condition of abnormal or excessive fat accumulation in adipose tissue, to the extent that health may be impaired,” and obesity is also defined as an adiposity-based chronic disease (ABCD). Obesity is a systemic disease that leads to metabolic abnormalities in various systems, resulting in a series of complications including obesity cardiomyopathy, atherosclerosis, nonalcoholic fatty liver disease, and diabetes mellitus. Emerging evidence shows that ferroptosis is closely associated with the occurrence and progression of various diseases. In recent years, ferroptosis has been found to play critical roles in obesity and its complications. This review discusses the mechanisms of how ferroptosis is initiated and controlled and discusses the research progress of ferroptosis in obesity and its complications.

Olive cake reduces obesity by decreasing epididymal adipocyte size, inhibiting oxidative stress and pancreatic lipase, in rat fed high fat diet

Purpose The purpose of this study is to investigate the effect of olive cake (OC) on oxidant/antioxidant biomarkers, lipase activity and on the histological analysis of epididymal fat, in high-fat diet (HFD)-induced obese rats. Design/methodology/approach Male obese rats were divided into two groups and were fed an HFD supplemented (HFD-OC) or not (HFD) with OC for 28 days. A control group was fed a standard diet for the same experimental period. Findings HFD significantly increased body weight, which was reduced by OC in the HFD-OC compared to HFD (p = 0.038). Lipase activity was higher (52%; p = 0.009) in the HFD group than the control group. Administration of OC to the obese rats decreased significantly this activity (38%; p = 0.025) compared to the HFD group. Serum thiobarbituric acid-reactive substances, lipid hydroperoxide and advanced oxidation protein products levels were significantly increased in the HFD group than the control group (p = 0.032, p = 0.023 and p = 0.017, respectively). These levels were significantly reduced in HFD-OC compared to the HFD group (p = 0.030, p = 0.021 and p = 0.010, respectively). Superoxide dismutase, glutathione peroxidase and catalase activities were decreased (53%; p = 0.04), (61%; p = 0.03) and (32%; p = 0.002), in the HFD group than the control group. OC restored these activities (46%; p = 0.01), (58%; p = 0.003) and (30%; p = 0.0003) in the HFD-OC rats than the HFD rats. Consumption of the HFD resulted in adipocyte hypertrophy. Indeed, epididymal adipocyte size was significantly larger in the HFD group than the control group (p = 0.0001), whereas it was reduced in the HFD-OC compared to the HFD group (p = 0.012). Originality/value OC possesses an anti-obesity effect. This effect might be mediated by lipase inhibition, reduced oxidative stress and increased antioxidant activities. In addition, the reduction of fat accumulation in adipose tissue by OC consumption is reflected by reducing adipocyte size.

Herbaceutical approach for the Management of Obesity, Oxidative Stress using Pennisetum Glaucum by invitro and insilico Models

Obesity is a condition in which there is excessive fat accumulation in adipose tissue, liver, skeletal muscle etc. It is a major concern for developing various disorders like type 2 diabetes, cardiovascular disease, hypertension, hyperlipidemia, atherosclerosis and cancer. In the present study, aqueous extract of Pennisetum glaucum seeds (AEPG) was screened for its anti-obesity and antioxidant activities by using in vitro models. Preliminary phytochemical analysis revealed the presence of flavonoids, tannins, phenols and carbohydrates. The pancreatic lipase inhibitory activity of the AEPG revealed its anti-obesity activity. Antioxidant activity of AEPG was performed by superoxide radical scavenging, hydrogen peroxide scavenging and hydroxyl radical scavenging activities, in which plant extract exhibited concentration dependent inhibitory action on respective free radicals. Pharmacokinetic studies i.e. in vitro ADME studies were also performed to components like Tricin, p-Coumaric acid and Syringic acid using Swiss ADME web tool. The ADME data of Tricin, p-Coumaric acid and Syringic acid suggest that these three molecules had good bioavailability score and which was further supported by their gastrointestinal absorption and good penetration power to the tissues. However further studies are required to establish its pharmacological actions in in vivo models and to isolate phytoconstituents that are actually responsible for antiobesity activity.

Amelioration of lipid accumulations and metabolism disorders in differentiation and development of 3T3-L1 adipocytes through mulberry leaf water extract

BackgroundObesity is a worldwide problem that resulted from the excessive fat accumulation in adipose tissue, leading to the impairment of individual health. Mulberry leaf is an important traditional Chinese medicine and has been used to alleviate obesity for a long term. However, its underlying molecular mechanisms have not been fully elucidated yet. PurposeIn this study, we aimed to investigate the inhibition effects of mulberry leaf water extract (MLWE) on lipid accumulation during the process of differentiation of 3T3-L1 preadipocytes and development of mature adipocytes through the combination of molecular biology assays and metabolomic analysis. MethodsThe quality consistency and main chemical ingredients of MLWE were analyzed by high performance liquid chromatography and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), respectively. Oil red O staining was used to mirror lipid accumulation. Lipogenesis-, lipolysis- and inflammation-related genes were evaluated by real-time PCR and western blot, respectively. Untargeted metabolomics were performed by LC-MS/MS. ResultsPrepared method and quality of MLWE were stable and reliable. A total of 34 compounds were identified and 14 of them were undoubtedly confirmed. MLWE supplementation could dose-dependently inhibit the aggregation of lipid droplets, and the expressions of sterol regulatory element-binding protein (SREBP)-1c, peroxisome proliferator-activated receptor (PPAR) γ, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increase the expressions of adenosine monophosphate-activated protein kinase (AMPK), hormone-sensitive lipase (HSL) and IL-10 in the differentiation of preadipocytes. Furthermore, MLWE treatment could dose-dependently decrease the level of triglycerides and the expressions of ACC, FAS, TNF-α, and IL-6, and up-regulate the level of glycerol and the expressions of PPARα, adiponectin (ADPN), adiponectin receptor (AdipoR) 1, AdipoR2, AMPK, HSL, and IL-10 in the development of mature adipocytes. Untargeted metabolomics showed that a total of 5 and 18 differential metabolites were reversed by MLWE intervention in the differentiation of preadipocytes and the development of mature adipocytes, respectively, which involved in the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism and glycerophospholipids metabolism. ConclusionTaken together, this study firstly verified that MLWE could effectively alleviate lipid accumulation and inflammation by regulating ADPN/AMPK-mediated signaling pathways and relevant metabolic disturbances including biosynthesis of unsaturated fatty acids, arachidonic acid metabolism and glycerophospholipids metabolism.