Obesity-related Metabolic Syndrome Research Articles

PPA1 promotes adipogenesis by regulating the stability of C/EBPs.

Adipogenesis significantly contributes to healthy adipose tissue expansion in obesity. Increasing adipocyte number or function to alleviate adipose tissue overload could serve as a therapeutic strategy for both lipodystrophy and obesity-related metabolic syndrome. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate (PPi) and is involved in many biochemical reactions, but its function in adipose tissue has not been studied previously. In this study, we demonstrated that adipose-specific PPA1 knockout (PPA1AKO) mice showed lipodystrophy and spontaneously developed hepatic steatosis and severe insulin resistance under normal chow diet feeding. PPA1 deficiency suppressed the differentiation of primary adipocyte precursors and 3T3-L1 cells. Notably, PPA1 overexpression can restore inhibited adipogenesis in preadipocytes isolated from db/db mice and type 2 diabetes patients. Mechanistic studies have revealed that PPA1 acts as a positive regulator of early adipocyte differentiation by promoting CCAAT/enhancer-binding proteinβ and δ (C/EBPβ and δ) protein stability. Moreover, the function of PPA1 in adipogenesis is independent of its PPi catalytic activity. Collectively, our in vivo and in vitro findings demonstrated that PPA1 is a novel critical upstream regulator of adipogenesis, controlling adipose tissue development and whole-body metabolic homeostasis.

Obesity and early-onset colorectal cancer risk: emerging clinical evidence and biological mechanisms.

Early-onset colorectal cancer (EOCRC) is defined as diagnosed at younger than 50 years of age and indicates a health burden globally. Patients with EOCRC have distinct risk factors, clinical characteristics, and molecular pathogenesis compared with older patients with CRC. Further investigations have identified different roles of obesity between EOCRC and late-onset colorectal cancer (LOCRC). Most studies have focused on the clinical characteristics of obesity in EOCRC, therefore, the mechanism involved in the association between obesity and EOCRC remains inconclusive. This review further states that obesity affects the carcinogenesis of EOCRC as well as its development and progression, which may lead to obesity-related metabolic syndrome, intestinal dysbacteriosis, and intestinal inflammation.

IRF8 aggravates nonalcoholic fatty liver disease via BMAL1/PPARγ axis

Non-alcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome arising from lipid metabolic imbalance, with its prevalence increasing globally. In this study, we observed a significant up-regulation of interferon regulatory factor 8 (IRF8) in the liver of NAFLD model mice and patients. Overexpression of IRF8 induced lipid accumulation in the mouse primary hepatocytes. Mice with adeno-associated virus-mediated IRF8 overexpression exhibited hepatic steatosis due to up-regulated peroxisome proliferator-activated receptor γ (PPARγ) expression and increased fatty acid uptake and lipogenesis. In vitro, small interfering RNA-mediated IRF8 knockdown attenuated triglyceride accumulation by dampening PPARγ expression through transcriptional inhibition of brain and muscle ARNT-like 1. The PPARγ-specific antagonist GW9662 abolished the effect of IRF8 overexpression. Furthermore, adeno-associated virus-mediated IRF8 knockdown in the mouse liver markedly alleviated hepatic steatosis and obesity-related metabolic syndrome. These findings indicate that IRF8 plays a vital role in modulating hepatic lipid metabolism in a PPARγ-dependent manner and provide a previously unknown insight into NAFLD therapeutic strategies.

Relevance of obesity-related organ damage and metabolic syndrome classification in cardiovascular and renal risk stratification in patients with essential hypertension.

Hypertension is a relevant cardiovascular comorbidity. Adipose tissue represents a metabolically active tissue involved in the regulation of blood pressure and metabolic alterations. In recent decades, several classifications for the metabolic syndrome (MS) have been proposed. Recently, a new syndrome called the "Cardiovascular-kidney-metabolic" (CKM) syndrome was identified, to determine patients at high cardiovascular and metabolic risk. The aim of the study was to compare different classifications in a large population of hypertensive patients. Between September 2022 and August 2023, we consecutively enrolled 772 hypertensive patients (407 men; 365 women; mean age 52.2 ± 15.1 years), evaluating anthropometric, biochemical, and instrumental parameters (transthoracic echocardiogram, carotid echo-Doppler, 24-h ambulatory blood pressure monitoring, fundus oculi). Using different classifications we found MS prevalence: Adult Treatment Panel III (ATP-III) 28.8%, International Diabetes Federation (IDF) 31.5%, CKM 40.7%. CKM Classes 3 and 4 showed higher body mass index and waist circumference compared with other groups. Compared with ATP-III and IDF, CKM Class 4 showed higher 24-h systolic blood pressure, lower percentage of controlled hypertension, increased interventricular septum and posterior wall, reduced ejection fraction, and greater prevalence of hypertensive arterial retinal damage. Visceral obesity and MS are frequent conditions with healthy impact, becoming an important trigger for the development of cardiovascular and metabolic complications. The different MS classifications allow the early identification of patients at high risk of cardiometabolic complications. The new CKM syndrome proves useful to identify individuals at high risk for CKM morbidity and mortality.

The Association between Functional Dyspepsia and Metabolic Syndrome-The State of the Art.

Functional dyspepsia is a common functional disorder of the gastrointestinal tract that is responsible for many primary care visits. No organic changes have been found to explain its symptoms. We hypothesize that modern lifestyles and environmental factors, especially psychological stress, play a crucial role in the high prevalence of functional dyspepsia and metabolic syndrome. While gastrointestinal tract diseases are rarely linked to metabolic disorders, chronic stress, obesity-related metabolic syndrome, chronic inflammation, intestinal dysbiosis, and functional dyspepsia have significant pathophysiological associations. Functional dyspepsia, often associated with anxiety and chronic psychological stress, can activate the neuroendocrine stress axis and immune system, leading to unhealthy habits that contribute to obesity. Additionally, intestinal dysbiosis, which is commonly present in functional dyspepsia, can exacerbate systemic inflammation and obesity, further promoting metabolic syndrome-related disorders. It is worth noting that the reverse is also true: obesity-related metabolic syndrome can worsen functional dyspepsia and its associated symptoms by triggering systemic inflammation and intestinal dysbiosis, as well as negative emotions (depression) through the brain-gut axis. To understand the pathophysiology and deliver an effective treatment strategy for these two difficult-to-cure disorders, which are challenging for both caregivers and patients, a psychosocial paradigm is essential.

Innovative high fat diet establishes a novel zebrafish model for the study of visceral obesity

Obesity is a complex chronic condition associated with multiple health risks, including visceral obesity, which is particularly detrimental. To gain insight into the mechanisms underlying obesity and its associated pathologies, a novel zebrafish model was established using an innovative high-fat diet (HFD). The primary goal was to induce visceral obesity in zebrafish and study the associated structural changes. To achieve this, a unique HFD consisting of 40% beef fat (HFD40) was developed and supplemented with magnesium aluminometasilicate to improve stability in a high humidity environment. Feeding regimens were initiated for both juvenile (starting at 2 weeks post-fertilization, lasting 18 weeks) and adult zebrafish (3 months post-fertilization, 8 weeks feeding duration). The innovative dietary approach successfully induced visceral obesity in both juvenile and adult zebrafish. This new model provides a valuable tool to study obesity-related pathologies, metabolic syndrome, and potential therapeutic interventions. Most importantly, the low-cost and easy-to-prepare composition of HFD40 was seamlessly incorporated into the water without the need for separation, was readily absorbed by the fish and induced rapid weight gain in the zebrafish population. In conclusion, this study presents a novel HFD40 composition enriched with a high beef fat concentration (40%), which represents a significant advance in the development of an experimental zebrafish model for the study of visceral obesity and associated metabolic changes.

Palmitoleic acid on top of HFD ameliorates insulin resistance independent of diacylglycerols and alters gut microbiota in C57BL/6J mice

With the prevalence of obesity and obesity-related metabolic syndrome, such as insulin resistance in recent years, it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome. Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources, mainly derived from marine products. Palmitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation. However, it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance. Here, we investigated the effects of palmitoleic acid on chow diet (CD)-fed and high-fat diet (HFD)-fed mice, which were fed CD or HFD for 12 weeks before administration. We administrated mice with BSA (control), oleic acid, or palmitoleic acid for 6 weeks on top of CD or HFD feeding. We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR. Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population. In colon, palmitoleic acid increased intestinal tight junction integrity and reduced inflammation. Moreover, palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue. Diacylglycerol (DAG) in tissue (for example, liver) is found to positively correlated with HOMA-IR. HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study. Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver. Therefore, in HFD-fed mice, palmitoleic acid reduced insulin resistance by an independent-manner of DAGs. It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition, improving of intestinal barrier function, and downregulating the inflammation in colon, liver, and adipose tissue.

Hepatic-Specific FGF21 Knockout Abrogates Ovariectomy-Induced Obesity by Reversing Corticosterone Production.

Increased glucocorticoid (GC) levels act as a master contributor to central obesity in estrogen-depleted females; however, what factors cause their increased GC production is unclear. Given (1) liver fibroblast growth factor 21 (FGF21) and GCs regulate each other's production in a feed-forward loop, and (2) circulating FGF21 and GCs are parallelly increased in menopausal women and ovariectomized mice, we thus hypothesized that elevation of hepatic FGF21 secretion causes increased GGs production in estrogen-depleted females. Using the ovariectomized mice as a model for menopausal women, we found that ovariectomy (OVX) increased circulating corticosterone levels, which in turn increased visceral adipose Hsd11b1 expression, thus causing visceral obesity in females. In contrast, liver-specific FGF21 knockout (FGF21 LKO) completely reversed OVX-induced high GCs and high visceral adipose Hsd11b1 expression, thus abrogating OVX-induced obesity in females. Even though FGF21 LKO failed to rescue OVX-induced dyslipidemia, hepatic steatosis, and insulin resistance. What's worse, FGF21 LKO even further exacerbated whole-body glucose metabolic dysfunction as evidenced by more impaired glucose and pyruvate tolerance and worsened insulin resistance. Mechanically, we found that FGF21 LKO reduced circulating insulin levels, thus causing the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes in OVX mice. Collectively, our results suggest that liver FGF21 plays an essential role in mediating OVX-induced central obesity by promoting GC production. However, lack of liver FGF21 signaling reduces insulin production and in turn causes the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes, highlighting a detrimental role for hepatic FGF21 signals in mediating the development of central obesity but a beneficial role in preventing metabolic abnormality from further exacerbation in estrogen-depleted females.

High-coverage genome of the Tyrolean Iceman reveals unusually high Anatolian farmer ancestry

The Tyrolean Iceman is known as one of the oldest human glacier mummies, directly dated to 3350-3120 calibrated BCE. A previously published low-coverage genome provided novel insights into European prehistory, despite high present-day DNA contamination. Here, we generate a high-coverage genome with low contamination (15.3×) to gain further insights into the genetic history and phenotype of this individual. Contrary to previous studies, we found no detectable Steppe-related ancestry in the Iceman. Instead, he retained the highest Anatolian-farmer-related ancestry among contemporaneous European populations, indicating a rather isolated Alpine population with limited gene flow from hunter-gatherer-ancestry-related populations. Phenotypic analysis revealed that the Iceman likely had darker skin than present-day Europeans and carried risk alleles associated with male-pattern baldness, type 2 diabetes, and obesity-related metabolic syndrome. These results corroborate phenotypic observations of the preserved mummified body, such as high pigmentation of his skin and the absence of hair on his head.

Contribution of environmental, genetic and epigenetic factors to obesity-related metabolic syndrome

Contribution of environmental, genetic and epigenetic factors to obesity-related metabolic syndrome

Dietary Supplementation of Cedryl Acetate Ameliorates Adiposity and Improves Glucose Homeostasis in High-Fat Diet-Fed Mice.

Cedryl acetate (CA), also called acetyl cedrene, is approved by the FDA as a flavoring or adjuvant to be added to foods. In this study, we aimed to investigate the preventive benefits of CA on obesity and obesity-related metabolic syndrome caused by a high-fat diet (HFD). Three groups of C57BL/6J mice (ten-week-old) were fed Chow, an HFD, or an HFD with CA supplementation (100 mg/kg) for 19 weeks. We observed that CA supplementation significantly reduced weight gain induced by an HFD, decreased the weight of the visceral fat pads, and prevented adipocyte hypertrophy in mice. Moreover, mice in the CA group showed significant improvements in hepatic lipid accumulation, glucose intolerance, insulin resistance, and gluconeogenesis compared with the mice in the HFD group. Since 16S rRNA analysis revealed that the gut microbiota in the CA and HFD groups were of similar compositions at the phylum and family levels, CA may have limited effects on gut microbiota in HFD-fed mice. The beneficial effects on the metabolic parameters of CA were reflected by CA's regulation of metabolism-related gene expression in the liver (including Pepck, G6Pase, and Fbp1) and the epididymal white adipose tissues (including PPARγ, C/EBPα, FABP4, FAS, Cytc, PGC-1α, PRDM16, Cidea, and COX4) of the mice. In summary, a potent preventive effect of CA on HFD-induced obesity and related metabolic syndrome was highlighted by our results, and CA could be a promising dietary component for obesity intervention.

Influenza vaccination in patients affected by diabetes.

Type 2 diabetes, obesity-related metabolic syndrome, and insulin resistance are the most common metabolic disorders associated with increased cardiovascular risk. In addition, patients with Type 2 diabetes have an increased risk for a more severe course of influenza virus infection, a common pandemic. There is increasing evidence that influenza vaccination in patients with diabetes can safely and effectively reduce all-cause mortality and cardiovascular death. The effects of vaccination appear to be more effective when using higher-dose and quadrivalent vaccines, although subgroup-specific separate analyses in patients with diabetes are lacking. Clinical recommendations address influenza vaccination in all adults with diabetes. From our point of view, it should be an integral part of treatment strategies in patients with diabetes.

Ponatinib modulates the metabolic profile of obese mice by inhibiting adipose tissue macrophage inflammation.

Obesity-induced metabolic syndrome is a rapidly growing conundrum, reaching epidemic proportions globally. Chronic inflammation in obese adipose tissue plays a key role in metabolic syndrome with a series of local and systemic effects such as inflammatory cell infiltration and inflammatory cytokine secretion. Adipose tissue macrophages (ATM), as one of the main regulators in this process, are particularly crucial for pharmacological studies on obesity-related metabolic syndrome. Ponatinib, a multi-targeted tyrosine kinase inhibitor originally used to treat leukemia, has recently been found to improve dyslipidemia and atherosclerosis, suggesting that it may have profound effect on metabolic syndrome, although the mechanisms underlying have not yet been revealed. Here we discovered that ponatinib significantly improved insulin sensitivity in leptin deficient obese mice. In addition to that, ponatinib treatment remarkably ameliorated high fat diet-induced hyperlipidemia and inhibited ectopic lipid deposition in the liver. Interestingly, although ponatinib did not reduce but increase the weight of white adipose tissue (WAT), it remarkably suppressed the inflammatory response in WAT and preserved its function. Mechanistically, we showed that ponatinib had no direct effect on hepatocyte or adipocyte but attenuated free fatty acid (FFA) induced macrophage transformation from pro-inflammatory to anti-inflammatory phenotype. Moreover, adipocytes co-cultured with FFA-treated macrophages exhibited insulin resistance, while pre-treat these macrophages with ponatinib can ameliorate this process. These results suggested that the beneficial effects of ponatinib on metabolic disorders are achieved by inhibiting the inflammatory phenotypic transformation of ATMs, thereby maintaining the physiological function of adipose tissue under excessive obesity. The data here not only revealed the novel therapeutic function of ponatinib, but also provided a theoretical basis for the application of multi-target tyrosine kinase inhibitors in metabolic diseases.

Metabolomics reveals inosine 5′-monophosphate is increased during mice adipocyte browning

Adipocyte browning is one of the potential strategies for the prevention of obesity-related metabolic syndromes, but it is a complex process. Although previous studies make it increasingly clear that several transcription factors and enzymes are essential to induce browning, it is unclear what dynamic and metabolic changes occur in induction of browning. Here, we analyzed the effect of a beta-adrenergic receptor agonist (CL316243, accelerator of browning) on metabolic change in mice adipose tissue and plasma using metabolome analysis and speculated that browning is regulated partly by inosine 5′-monophosphate (IMP) metabolism. To test this hypothesis, we investigated whether Ucp-1, a functional marker of browning, mRNA expression is influenced by IMP metabolism using immortalized adipocytes. Our study showed that mycophenolic acid, an IMP dehydrogenase inhibitor, increases the mRNA expression of Ucp-1 in immortalized adipocytes. Furthermore, we performed a single administration of mycophenolate mofetil, a prodrug of mycophenolic acid, to mice and demonstrated that mycophenolate mofetil induces adipocyte browning and miniaturization of adipocyte size, leading to adipose tissue weight loss. These findings showed that IMP metabolism has a significant effect on adipocyte browning, suggesting that the regulator of IMP metabolism has the potential to prevent obesity.

Metabolic status is not related to dietary acid load in polycystic ovary syndrome

Aim:Women with polycystic ovary syndrome (PCOS) are at high risk for obesity-related disorders, insulin resistance (IR), and metabolic syndrome (MS). Adopting potent approaches to diet enhances cardiometabolic risk profile and reproductive function. Different types of diets have provided conflicting results so far. We aimed to investigate whether dietary acid load (DAL) contributed to the metabolic process in PCOS.
 Material and Method: This study included 46 newly diagnosed PCOS patients and 46 healthy individuals with matched age, sex, and BMI. Clinical, anthropometric, and biochemical measurements were obtained. We extracted net endogenous acid production (NEAP) and potential renal acid load (PRAL) scores from 24-hour dietary data recorded on a nutrient database program for three days (BeBiS software program).
 Results:We concluded no statistically significant difference between the groups by NEAP (p=0.569) and PRAL (p=0.969).Patients with PCOS had higher fasting insulin levels and HOMA-IR (p

Performance of body mass index and body fat percentage in predicting metabolic syndrome risk factors in diabetic patients of Yazd, Iran

BackgroundBody Fat percentage (BFP) and body mass index (BMI) are used to measure obesity-related metabolic syndrome risk. The present study aimed to determine the values of percent body Fat and body mass index for predicting metabolic syndrome risk factors in diabetic patients of Yazd, Iran.MethodsA total of 1022 (499 males and 523 females) diabetic patients participated in this study. According to Asian BMI criteria, Overweight was diagnosed if a participant had a BMI ≥25 kg/m2 (both male and female) or BFP ≥25% for male and ≥ 32% for female. Based on calculated BMI and BFP and after adjusting for age, height, weight and smoking habits, the participants were classified into group A (normal weight and Non-Fat), group B (overweight and Non-Fat), group C (normal weight and Fat), and group D (overweight and Fat).ResultsAccording to the results, the BMI of 23.4% were normal and BMI of 76.6% were overweight, respectively. Moreover, the BFP of 25.7 and 74.3% of the studied population were considered as Non-Fat and Fat, respectively. A strong relationship was found with respect to sex stratification; R2 = 0.79. For men, BMI can be a better predictor of hypertension and hypertriglyceridemia than BFP. For women, BMI was a better predictor of hyperglycemia than BFP. Moreover, BFP can be regarded as a better predictor of hyperglycemia in male group, while it was a good predictor of hypertension and hypertriglyceridemia and hypo HDL than BMI, in female group.ConclusionSignificant differences were observed between BMI and BFP to predict metabolic syndrome risk factors in diabetic patients across different sexes in our study population. In conclusion, both BMI and BFP should be considered in screening steps.

Abstract P2015: Metabolic-epigenetic Coupling In High Fat Diet And Heart Failure With Reduced Ejection Fraction

Given rising obesity rates, understanding how metabolic changes exacerbate other cardiovascular disease (CVD) risk factors will yield novel therapeutic targets for associated comorbidities, such as heart failure. We hypothesize that obesity-related metabolic syndrome induces transcriptional programs that engender cardiac pathology via mechanisms involving chromatin regulators, thereby perpetuating the pathology by epigenetic memory. C57BL/6J adult male mice were put on a high fat diet (HFD) for 24 weeks. After HFD, hearts were in hypertrophy, as defined by an increase in heart weight to tibia length ratio (24.67 ± 5.14 mg/mm in HFD versus 17.06 ± 0.98 mg/mm in regular chow controls, p=0.026). Examination of blood plasma revealed significant increase in LDL-C (74.37 ± 22.45 mg/dL in HFD versus 21.91 ± 5.98 mg/dL in controls, p=0.0005) and insulin (452.81 ± 224.77 uIU/mL in HFD versus 89.66 ± 45.60 uIU/mL in controls, p=0.0003), indicative of metabolic disorder. RNA-seq of isolated cardiomyocytes revealed distinct transcriptomic changes at 1 week, 6 weeks, and 24 weeks of HFD. At 1 week, HFD stimulus induced promotion of lipid metabolism ( Pdk4, Per2 ) and suppression of genes related to development and proliferation ( Sox4, Epha4 ). By 6 weeks, the cardiomyocytes underwent metabolic reprogramming (downregulation of Lpl and Irs2 ) and structural changes ( Acta2, Col8a1). At 24 weeks, we observed suppression of ketolytic machinery (downregulation of Abat, Bdh1, and Oxct1 ) in response to obesity-driven hyperglycemia, suggesting that cardiomyocytes transitioned to a pre-diabetic state. To test whether this metabolic disease state compounds with other CVD risk factors, we devised a two-hit model, where mice were fed HFD for 6 weeks and then underwent transverse aortic constriction as a model of pressure overload. Cardiomyocytes from this two-hit model exhibited an enhanced hypertrophic response ( Myh7, Nppa, Col1a1 mRNA levels) compared to pressure overload with regular chow, sham surgery with HFD, or sham surgery with chow. Thus, phenotypic and transcriptional data suggest that HFD reprograms cardiomyocytes to a pre-diabetic state characterized by insulin resistance which exacerbates the effects of other CVD risk factors like hypertrophy.

Metabolic Syndrome and Obesity-Related Indices Are Associated with Rapid Renal Function Decline in a Large Taiwanese Population Follow-Up Study.

A rapid decline in renal function can cause many complications, and therefore it is important to detect associated risk factors. Few studies have evaluated the associations among obesity-related indices and metabolic syndrome (MetS) with renal function decline. This longitudinal study aimed to explore these relationships in a large cohort of Taiwanese participants. The studied obesity-related indices were waist-to-height ratio (WHtR), A body shape index (ABSI), visceral adiposity index (VAI), lipid accumulation product (LAP), waist-to-hip ratio (WHR), body roundness index (BRI), conicity index (CI), body mass index (BMI), body adiposity index (BAI) and abdominal volume index (AVI). We included 122,068 participants in the baseline study, of whom 27,033 were followed for a median of four years. The baseline prevalence of MetS was 17.7%. Multivariable analysis showed that the participants with MetS and high VAI, WHtR, WHR, LAP, CI, BRI, BMI, BAI, AVI, and ABSI values were significantly associated with a high baseline estimated glomerular filtration rate (eGFR) (all p < 0.001). In addition, the participants with MetS (p < 0.001), high WHtR (p = 0.007), low LAP (p < 0.001), high BRI (p = 0.002), high CI (p = 0.002), high AVI (p = 0.001), high VAI (p = 0.017), and high ABSI (p = 0.013) were significantly associated with a low △eGFR, indicating a rapid decline in renal function. These results showed associations between MetS and high values of obesity-related indices except LAP with high baseline eGFR and rapid decline in kidney function. These findings suggest that screening for MetS and obesity may help to slow the decline in renal function in high-risk populations.

Leonurine Attenuates Obesity-Related Vascular Dysfunction and Inflammation.

Oxidative stress in adipose tissue is a crucial pathogenic mechanism of obesity-associated cardiovascular diseases. Chronic low-grade inflammation caused by obesity increases ROS production and dysregulation of adipocytokines. Leonurine (LEO) is an active alkaloid extracted from Herba Leonuri and plays a protective role in the cardiovascular system. The present study tested whether LEO alleviates inflammation and oxidative stress, and improves vascular function in an obese mouse model. Here, we found that obesity leads to inflammation and oxidative stress in epididymal white adipose tissue (EWAT), as well as vascular dysfunction. LEO significantly improved inflammation and oxidative stress both in vivo and in vitro. Obesity-induced vascular dysfunction was also improved by LEO as evidenced by the ameliorated vascular tone and decreased mesenteric artery fibrosis. Using mass spectrometry, we identified YTHDF1 as the direct target of LEO. Taken together, we demonstrated that LEO improves oxidative stress and vascular remodeling induced by obesity and targets YTHDF1, raising the possibility of LEO treating other obesity-related metabolic syndromes.

A long-term anti-inflammation markedly alleviated high-fat diet-induced obesity by repeated administrations of overexpressing IL10 human umbilical cord-derived mesenchymal stromal cells

ObjectivesObesity is a chronic process and could activate various inflammatory responses, which in turn aggravates obesity and related metabolic syndrome. Here we explored whether long-term inhibition of inflammation could successfully alleviate high-fat diet (HFD)-induced obesity.MethodsWe constructed stable overexpressing interleukin 10 (IL10) human umbilical cord-derived mesenchymal stromal cells (HUCMSCs) which repeatedly were applied to obesity mice with HFD feeding to obtain a long-term anti-inflammation based on the prominent anti-inflammation effects of IL10 and immunomodulatery effects of HUCMSCs. Then we monitored the features of obesity including body weight, serum ALT, AST, and lipids. In addition, glucose homeostasis was determined by glucose tolerance and insulin sensitivity tests. The infiltrated macrophages in adipose tissues and hepatic lipid accumulation were detected, and the expressions of adipogenesis and inflammatory genes in adipose tissues were examined by real-time (RT) PCR and western blot analysis.ResultsCompared with HUCMSCs, IL10-HUCMSCs treatment had much better anti-obesity effects including body weight reduction, less hepatic lipids accumulation, lower amount and size of adipocyte, greater glucose tolerance, less systemic insulin resistance, and less adipose tissue inflammation in HFD feeding mice. Finally, IL10-HUCMSCs could decrease the activation of MAPK JNK of adipose tissue induced by HFD. The inhibition of MAPK JNK signal pathway by a small chemical molecule SP600125 in 3T3-L1 cells, a preadipocyte line, reduced the differentiation of adipocytes and lipid droplet accumulation.ConclusionA lasting anti-inflammation based on gene modified stem cell therapy is an effective strategy in preventing diet-induced obesity and obesity-related metabolic syndrome.