Aspects Of Metabolic Syndrome Research Articles

Liver Fat Storage Is a Better Predictor of Coronary Artery Disease than Visceral Fat.

Fatty liver is one aspect of metabolic syndrome. The roles and contributions of fatty liver and visceral fat storage to coronary artery disease (CAD) are not clear. This study measured associations among visceral fat storage, fatty liver, insulin resistance, atherosclerosis, and CAD. Patients were divided into three groups: excess visceral fat (visceral fat area >330 ± 99 cm2), non-alcoholic fatty liver disease (NAFLD), and a control group. The definition of fatty liver is liver minus spleen density greater than or equal to -10. We defined early atherosclerosis as intima-media thickness of the common carotid artery >7 mm in men and >0.65 mm in women, measured with Doppler ultrasound. Visceral fat area was defined using CT (>330 ± 99 cm2). Insulin-resistance biomarkers (HOMA), CRP, and oxidant-antioxidant status (MDA-Paraoxonase) were also measured. Patients with high liver or visceral fat showed higher coronary plaque prevalence (50% (p < 0.001), 38% (p < 0.01), respectively vs. 25% in the control group), higher prevalence of coronary stenosis (30% (p < 0.001), 22% (p < 0.01) vs. 11% in the control group), higher intimal thickening (0.98 ± 0.3 (p< 0.01), 0.86 ± 0.1 (p < 0.01) vs. 0.83 ± 0.1 in the control group), higher HOMA (4.0 ± 3.0 (p < 0.005), 3.0 ± 1.0 (p < 0.001) vs. 1.5 ± 1.2 in the control group), and higher triglyceride levels (196.8 ± 103 (p < 0.005), 182.6 ± 90.87 (p < 0.005) vs. 145 ± 60 in the control group). Multiple logistic regression analysis showed that fatty liver predicted CAD (OR 2.7, 95% CI 2.3-4.9, p < 0.001) independently of visceral fat storage (OR 2.01, 95% CI 1.2-2.8, p < 0.001). Liver fat storage is a strong independent risk factor for CAD and carotid atherosclerosis and contributes more than visceral fat storage.

Altered local RAS in the liver increased the risk of NAFLD in male mouse offspring produced by in vitro fertilization

BackgroundAssisted reproductive technology (ART) is associated with an increased risk of adverse metabolic health in offspring, and these findings have been demonstrated in animal models without parental infertility issues. However, it is unclear what changes lead to abnormal metabolism. The activation of the renin-angiotensin system (RAS) has been related to various aspects of metabolic syndrome. Thus, we focused on the local RAS of the liver, which is the central organ for glucose and lipid metabolism in offspring conceived by in vitro fertilization (IVF), and studied the role of local liver RAS in metabolic diseases.MethodsMale C57BL/6 mouse offspring obtained by natural pregnancy and IVF were fed a standard chow diet or a high-fat diet (HFD) from 4 weeks of age through 16 weeks of age. We assessed glucose and lipid metabolism, hepatic histopathology, and the gene and protein expression of key RAS components. In addition, the blocker losartan was used from 4 weeks of age through 16 weeks of age to investigate the regulatory mechanisms of abnormal local RAS on metabolic activity in the IVF offspring liver.ResultsThe growth trajectories of IVF offspring body and liver weights were different from those of naturally pregnant offspring. Impaired glucose tolerance (IGT) and insulin resistance (IR) occurred in IVF-conceived male offspring. After continuous HFD feeding, male offspring in the IVF group underwent earlier and more severe IR. Furthermore, there was a trend of lipid accumulation in the livers of chow-fed IVF offspring. Hepatic steatosis was also more serious in the IVF offspring after HFD treatment. Type 1 receptor (AT1R), which is the primary receptor mediating the action of angiotensin (Ang) II, has been confirmed to be upregulated in IVF offspring livers. Losartan reduced or even eliminated most of the significant differences between the IVF and NC groups after HFD consumption.ConclusionsThe upregulation of AT1R expression in the liver increased the activity of the local RAS, resulting in abnormal glucose and lipid metabolism and lipid accumulation in the liver, significantly increasing the risk of nonalcoholic fatty liver disease (NAFLD) in IVF offspring.

A Study Of Prevalence Of Chronic Kidney Disease In Patients With Metabolic Syndrome In Urban Population Attending A Tertiary Care Center In India: A Hospital-Based Prospective Cross-Sectional Observational Study

The study aims to determine the prevalence of Chronic Kidney Disease (CKD) and its risk factors in patients with Metabolic Syndrome in a tertiary care center in India. It was a hospital-based prospective observational study where NCEP ATP III CRITERIA was used to diagnose patients with Metabolic Syndrome, and CKD was defined according to KDIGO Guidelines. Out of 172 patients with Metabolic Syndrome, CKD was seen in 52 patients, of which 29 were males and 23 were females, so the prevalence of CKD in Metabolic Syndrome patients was about 30.23%. (52/172) P Value = 0.0000204. In our study, the prevalence of hyperglycemia in CKD patients with Metabolic Syndrome was 24.41% (42/172) P Value = .0011. The prevalence of obesity was 19.18% (33/172) P Value = .00844. The prevalence of hypertension was 28.48% (49/172) P Value = 2.72. The prevalence of hypertriglyceridemia was 26.12% (45\172) P Value = 0.000002086. The prevalence of hyperglycemia, obesity, and hypertriglyceridemia was significantly high in males. The prevalence of CKD in Metabolic Syndrome is 30.23% which is quite high, and since the prevalence of CKD is rising in India, we need more studies to look into this aspect of Metabolic Syndrome.

Prevalence of Metabolic Syndrome in Young Patients with Acute ST Elevation Myocardial Infarction (STEMI)

Background: The metabolic syndrome is linked to several conventional and rising pro-thrombotic and pro-inflammatory cardiac risks. Most patients with cardiovascular disease have metabolic syndrome; however, the occurrence and connection of its various elements aren't obvious. There isn't any research regarding the occurrence of Metabolic Syndrome in young patients with acute STEMI. Objective: The purpose of this study was to figure out the occurrence of metabolic syndrome (MS) in young patients shown ST-Elevation Myocardial Infarction (STEMI) at a tertiary care hospital in Karachi, Pakistan. Material and Methods: The research was conducted on 170 patients with STEMI. Body mass index was measured. Smoking level, metabolic syndrome (MS), and aspects of the metabolic syndrome (BMI &gt;23 kg meter per square, high blood pressure, hypertriglyceridemia, low-plasma HDLc, and affected fasting plasma glucose) were noted. Descriptive statistics were used, and stratification was done in the study. Fisher exact test and post-stratification by square test were used during the research study. P-value ≤0.05 was regarded as significant. Results: There were 42.2% women and 57.6% men with a mean age of 29.84±7.96 years. Metabolic syndrome (MS) was positive in 64.7 per cent of sufferers. BMI &gt;23 kg meter per square was noticed in 97.1 per cent of patients. High blood pressure in 72.4 per cent of patients. Hypertriglyceridemia in 77.65 per cent of patients, Low plasma HDLc in 44.1 per cent of individuals, and affected fasting plasma glucose in 47.1 per cent of patients. Conclusion: It had been determined by research findings that the occurrence of metabolic syndrome in young patients having STEMI was higher. The common element was BMI &gt;23 kg/m2, Hypertension, and Hypertriglyceridemia. Keywords: Prevalence, Young Patients, Metabolic Syndrome (MS), STEMI, Aspects of MS

Depression and Metabolic Syndrome: A Narrative Review.

We reviewed the literature to investigate the relationship between depression and metabolic syndrome. Major depressive disorder is characterized by a low mood or a loss of interest for longer than two weeks. Metabolic syndrome describes multiple metabolic risk factors including obesity, insulin resistance, dyslipidemia, and hypertension. We divided our findings into environmental, genetic, epigenetic, and biological pathway links between depression and the different aspects of metabolic syndrome. We found various sources linking obesity and metabolic syndrome genetically, environmentally, biological pathway-wise, and, while not fully explored, epigenetically. Diabetes and depression were also found to be linked environmentally with both conditions increasing the risk of the other. Depression was also shown to be linked to cardiovascular complications as it increased the risk of occurrence of such complications in healthy people. These findings have led us to believe that there is a link between depression and metabolic syndrome on various levels, especially obesity.

Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and is often associated with aspects of metabolic syndrome. Despite its prevalence and the importance of early diagnosis, there is a lack of robustly validated biomarkers for diagnosis, prognosis and monitoring of disease progression in response to a given treatment. In this Review, we provide an overview of the contribution of metabolomics and lipidomics in clinical studies to identify biomarkers associated with NAFLD and nonalcoholic steatohepatitis (NASH). In addition, we highlight the key metabolic pathways in NAFLD and NASH that have been identified by metabolomics and lipidomics approaches and could potentially be used as biomarkers for non-invasive diagnostic tests. Overall, the studies demonstrated alterations in amino acid metabolism and several aspects of lipid metabolism including circulating fatty acids, triglycerides, phospholipids and bile acids. Although we report several studies that identified potential biomarkers, few have been validated.

Serum Biomarkers are Associated With Atherosclerotic Cardiovascular Disease Among Patients With Nonalcoholic Fatty Liver Disease Undergoing Elective Angiography

Cardiovascular disease is the most common cause of death among patients with nonalcoholic fatty liver disease (NAFLD). We assessed select cardiac biomarker associations for existing or future coronary artery disease (CAD) risk in patients with NAFLD. Patients with/without NAFLD undergoing elective cardiac angiography were prospectively enrolled. Severe CAD was defined as presence of at least 1 proximal artery >70% stenosis; risk of severe CAD as either existing severe CAD or atherosclerotic cardiovascular disease score ≥20; NAFLD was defined as hepatic fat in the absence of other liver diseases. Cardiac biomarkers (high-sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and high-sensitivity cardiac troponin I [hs-cTnI]) were measured using Atellica Solution assays (Siemens Healthineers). A total of 619 patients were enrolled (mean age, 63 ± 10 years; 80% male; 31% type 2 diabetes; 65% NAFLD); 42% had severe CAD, and 57% had risk of severe CAD. NAFLD prevalence was similar between patients with and without severe CAD (68% vs 62%; P > .05). Patients with NAFLD with severe CAD (44%) or with risk of severe CAD (58%) had higher levels of hs-cTnI than NAFLD controls (both P < .001). Presence of severe CAD or risk of severe CAD in all patients was associated with older age, male, aspects of metabolic syndrome, and elevated hs-cTnI: odds ratio 2.0 (95% confidence interval [CI],1.4-2.9) and 1.8 (95% CI, 1.1-3.0), respectively; 2.3 (95% CI, 1.4-3.8) and 2.2 (95% CI, 1.2-4.2), respectively, in patients with NAFLD (all P < .02). CAD is common in patients with NAFLD. High hs-cTnI was associated with an increased risk of CAD. Pending validation, hs-cTnI may be a useful marker for CAD risk prediction in patients with NAFLD.

Differential and shared effects of eicosapentaenoic acid and docosahexaenoic acid on serum metabolome in subjects with chronic inflammation

The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect cell function and metabolism, but the differential effects of EPA and DHA are not known. In a randomized, controlled, double-blind, crossover study, we assessed the effects of 10-week supplementation with EPA-only and DHA-only (3 g/d), relative to a 4-week lead-in phase of high oleic acid sunflower oil (3 g/day, defined as baseline), on fasting serum metabolites in 21 subjects (9 men and 12 post-menopausal women) with chronic inflammation and some characteristics of metabolic syndrome. Relative to baseline, EPA significantly lowered the tricarboxylic acid (TCA) cycle intermediates fumarate and α-ketoglutarate and increased glucuronate, UDP-glucuronate, and non-esterified DHA. DHA significantly lowered the TCA cycle intermediates pyruvate, citrate, isocitrate, fumarate, α-ketoglutarate, and malate, and increased succinate and glucuronate. Pathway analysis showed that both EPA and DHA significantly affected the TCA cycle, the interconversion of pentose and glucuronate, and alanine, and aspartate and glutamate pathways (FDR < 0.05) and that DHA had a significantly greater effect on the TCA cycle than EPA. Our results indicate that EPA and DHA exhibit both common and differential effects on cell metabolism in subjects with chronic inflammation and some key aspects of metabolic syndrome.

The importance of prebiotics in the regulation of metabolic syndrome disorders

The products of functional foods differ from other meals by their ability to improve health and well‑being or to reduce the risk of diseases and not only to provide the good nutrition. The composition of such products includes oligosaccharides of the fructan type such as inulin. Inulin is a soluble dietary fiber, consisting of a group of natural polysaccharides that are not digested in the intestine and instead fermented into short‑chain fatty acids associated with multiple metabolic processes, including glucose homeostasis and insulin resistance. Besides, inulin affects the lipid exchange regulation and improvement of lipid profile. Inulin is a mixture of linear fructose polymers or fructans with 2 — 60 units, each of them is connected by unique β (2‑1) bonds with a glucose unit. In contrary to typical carbohydrate, these β (2‑1) connections cannot be hydrolyzed by enzymes of saliva or pancreas, that’s why inulin has a reduced energetic value as well as dietary prebiotic effects.Functional food is an important component of the change in the lifestyle to control obesity and related risks for health. Obesity and dyslipidemia are important aspects of metabolic syndrome, associated with changes in the gut microbiome. The most important direction in the modern preventive and therapeutic medicine presents the use of prebiotics, that provide positive effects on the normal microflora and cause a whole cascade of secondary beneficial effects for humans (metabolic, anticarcinogenic, immunostimulating, antitoxic, etc.). Prebiotic Inulin promotes the restoration of intestinal microbiome by means of increasing production of intestinal epithelial cells and recovering interleukin‑22 expression.On the domestic market inulin presented as an Inulin‑NEO preparation, available in a form of tablets and sachet, which makes it easy to use.

ASSOCIATION OF SERUM MAGNESIUM LEVEL WITH RESISTANT HYPERLIPIDEMIA IN DIABETIC AND HYPERTENSIVE PATIENTS

Introduction: Both diabetes mellitus and hypertension are aspects of metabolic syndrome. Objectives: The aim of this study was to determine the relationship between serum magnesium level with resistant hyperlipidemia in a group of diabetic and hypertensive patients. Patients And Methods: The present cross- sectional study was carried out on 90 hypertensive and diabetic patients in Medicine Department of DMCH, Laheriasarai, Bihar, (45 hypertensive and 45 diabetic patients). Included patients had high triglyceride levels despite 8 weeks of treatment with lipid-lowering agents. Results: There was an inverse signicant relationship between serum magnesium and triglyceride levels in diabetic patients (P=0.002, r=-0.458), however, this correlation was not signicant in hypertensive patients (P=0.754, r=0.048). Conclusion: This study showed, serum magnesium may affect triglycerides levels in diabetic patients, however, our nding requires further investigation with larger population

High-fat, high-carbohydrate diet-induced experimental model of metabolic syndrome in rats

Purpose. The study is focused on development of high-fat, high-carbohydrate diet-induced experimental model of metabolic syndrome (MS) in rats. Materials and methods. The 6-week old Wistar rats ( n = 20) were used for study. Rats were separated into control and experimental groups. The rats from the control group were fed standard rat chow. The rats from the experimental group had a high-fat, high-carbohydrate diet rich in lard (17%) and fructose (17%) and drank 20% fructose solution. At the end of the study, body weight and blood pressure (BP) were assessed. After 12 weeks of a diet load, an oral glucose tolerance test (GTT) and insulin tolerance test (ITT) were carried out. Lipid and protein biochemical parameters in plasma were analyzed. Adipose tissue and liver were measured at the end of the study. The levels of triacylglycerol (TAG) and cholesterol (Сh) in the liver were determined by enzymatic methods. Results. High-fat, high-carbohydrate diet feeding in rats for 12 weeks led to BP elevation and increase in the adipose tissue/body weight ratio. Hyperglycemia, impaired glucose tolerance and insulin resistance were found in rats with MS by means of GTT and ITT. Elevation of plasma TAG level was observed in the experimental group, although plasma total Сh and HDL-Ch did not differ from those of controls. Liver/body weight ratio and the level of TAG and Ch in the liver were elevated in rats with MS. Conclusion. Experimental rat model of diet-induced MS reproduces many aspects of MS in humans. This model may be useful for studying the pathophysiology of MS and methods for its prevention and treatment.

Correlating Circulating Vitamin D3 with Aspects of the Metabolic Syndrome and Nonalcoholic Fatty Liver Disease in Healthy Female Volunteers

Background: Significant inverse correlations between circulating vitamin D3 and the presence and strength of common clinical entities influenced by insulin resistance (IR) have been reported. Among these entities are common maladies such as the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD). Since hypovitaminosis D3 is considered a common worldwide health disturbance, the consequences emanating from such relationships once soundly established might reasonably be ameliorated by vitamin replacement. Accordingly, a need exists for definitive confirmatory support for the existence of these linkages particularly in ordinary, relatively healthy individuals.Methodology: Many aspects of MS and NAFLD were examined in healthy females via linear regression analyses to determine significant correlations mainly using vitamin D3 and fasting blood glucose (FBG), the latter a surrogate for IR, as independent variables.Results: A descending linear regression between vitamin D3 and FBG did not reach full statistical significance, but a negative correlation of vitamin D3 with HbA1C was statistically significant and that with circulating insulin concentrations showed a downward statistical trend. These findings are consistent with previous ones by others suggesting an ameliorating effect of vitamin D3 on IR. Body weight, body mass index (BMI), and body fat correlated statistically significantly with vitamin D3 levels, as did systolic blood pressure. Again, these correlations were negative instead of positive unlike the case when FBG was the independent variable. The significant negative correlation of ALT with vitamin D3 was also consistent with previous reports that higher circulating vitamin D3 favorably influences the extent and intensity of NAFLD.Conclusions: Employing FBG as a surrogate for IR and ALT for status of NAFLD, linear correlations reasonably suggest that increasing circulating vitamin D3 can favorably influence the initial development of and/or strength of risk factors for MS including NAFLD in relatively fit females.

A non-pharmacological therapeutic approach in the gut triggers distal metabolic rewiring capable of ameliorating diet-induced dysfunctions encompassed by metabolic syndrome

Metabolic syndrome has increased at a worrisome level. Lifestyle changes are not sufficient to prevent and improve the adverse effects of obesity, thus novel interventions are necessary. The aim of this study was to investigate the use and metabolic outcomes of a non-pharmacological intervention in a high-fat diet (HFD) fed mouse model, capable of recapitulating key aspects of metabolic syndrome. We show that Policaptil Gel Retard has remarkable, beneficial effects on metabolic dysfunction caused by consumption of HFD. We describe the mechanism by which such effects are obtained, highlighting the fact that the amelioration of metabolic function observed upon Policaptil Gel Retard administration is profound and of systemic nature, despite being originated by sequestering, therefore non-pharmacological events elicited in the gut lumen.

Evaluation of metabolic syndrome in undergraduate students at the University of Dschang

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases (CVD), such as obesity, dyslipidemia, high blood pressure, and high blood glucose; it increases morbidity and mortality of CVD. MetS affects both adults and youths, leading to an impaired quality of life and a lowering of life expectancy. This study aimed to assess various aspects of metabolic syndrome, in undergraduate students at the University of Dschang. A questionnaire was distributed to 307 students of both sex; 203 meeting inclusion criteria were selected for anthropometric and blood pressure measurements followed by blood sample collection, for the dosage of biochemical markers (blood glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceridemia, and C-reactive protein). Results indicate that the prevalence of metabolic syndrome within the study population was 11.33 %. It has a significant predominance among obese and overweight patients (P˂0.05), compared to normal ones. Elevated blood pressure (OR= 23.4) and low HDL cholesterol levels (OR= 20.4) appeared to be the most determinant components of metabolic syndrome in the study population. We found an increase of metabolic syndrome prevalence with frequent consumption (3 to 4 times per week) of ‘‘Koki’’ (P=0.023), ‘‘Achu’’ (P=0.01), ‘’Corn couscous’’ (P=0.012), Salads (P=0.031), ‘‘Ndole’’ (P=0.039) and pork (P=0.04). On the contrary, the prevalence of metabolic syndrome decreases significantly, with frequent consumption of green vegetables (P=0.016). Metabolic syndrome is present in undergraduate students of the University of Dschang, as a consequence of excess fat storage. Its main features are elevated blood pressure and low HDL-cholesterol level.Keywords: Obesity; Metabolic syndrome; cardiovascular risk factor; students; University of Dschang

"Western Diet"-Induced Adipose Inflammation Requires a Complex Gut Microbiota.

Background & AimsConsumption of a low-fiber, high-fat, Western-style diet (WSD) induces adiposity and adipose inflammation characterized by increases in the M1:M2 macrophage ratio and proinflammatory cytokine expression, both of which contribute to WSD-induced metabolic syndrome. WSD-induced adipose inflammation might result from endoplasmic reticulum stress in lipid-overloaded adipocytes and/or dissemination of gut bacterial products, resulting in activation of innate immune signaling. Hence, we aimed to investigate the role of the gut microbiota, and its detection by innate immune signaling pathways, in WSD-induced adipose inflammation.MethodsMice were fed grain-based chow or a WSD for 8 weeks, assessed metabolically, and intestinal and adipose tissue were analyzed by flow cytometry and quantitative reverse transcription polymerase chain reaction. Microbiota was ablated via antibiotics and use of gnotobiotic mice that completely lacked microbiota (germ-free mice) or had a low-complexity microbiota (altered Schaedler flora). Innate immune signaling was ablated by genetic deletion of Toll-like receptor signaling adaptor myeloid differentiation primary response 88.ResultsAblation of microbiota via antibiotic, germ-free, or altered Schaedler flora approaches did not significantly impact WSD-induced adiposity, yet dramatically reduced WSD-induced adipose inflammation as assessed by macrophage populations and cytokine expression. Microbiota ablation also prevented colonic neutrophil and CD103- dendritic cell infiltration. Such reduced indices of inflammation correlated with protection against WSD-induced dysglycemia, hypercholesterolemia, and liver dysfunction. Genetic deletion of myeloid differentiation primary response 88 also prevented WSD-induced adipose inflammation.ConclusionsThese results indicate that adipose inflammation, and some aspects of metabolic syndrome, are not purely a consequence of diet-induced adiposity per se but, rather, may require disturbance of intestine-microbiota interactions and subsequent activation of innate immunity.

Association of serum magnesium level with resistant hyperlipidemia in diabetic and hypertensive patients

Introduction: Both diabetes mellitus and hypertension are aspects of metabolic syndrome. Objectives: The aim of this study was to determine the relationship between serum magnesium level with resistant hyperlipidemia in a group of diabetic and hypertensive patients. Patients and Methods: The present cross-sectional study was carried out on 90 hypertensive and diabetic patients who referred to outpatient university clinic in Shahrekord (45 hypertensive and 45 diabetic patients). Included patients had high triglyceride levels despite 8 weeks of treatment with lipid-lowering agents. Results: There was an inverse significant relationship between serum magnesium and triglyceride levels in diabetic patients (P=0.002, r=-0.458), however, this correlation was not significant in hypertensive patients (P=0.754, r=0.048). Conclusion: This study showed, serum magnesium may affect triglycerides levels in diabetic patients, however, our finding requires further investigation with larger population.

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases.

Fatty acid-binding proteins (FABPs), a family of lipid chaperones, contribute to systemic metabolic regulation via several lipid signaling pathways. Fatty acid-binding protein 4 (FABP4), known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays important roles in the development of insulin resistance and atherosclerosis in relation to metabolically driven low-grade and chronic inflammation, referred to as ‘metaflammation’. FABP4 is secreted from adipocytes in a non-classical pathway associated with lipolysis and acts as an adipokine for the development of insulin resistance and atherosclerosis. Circulating FABP4 levels are associated with several aspects of metabolic syndrome and cardiovascular disease. Ectopic expression and function of FABP4 in cells and tissues are also related to the pathogenesis of several diseases. Pharmacological modification of FABP4 function by specific inhibitors, neutralizing antibodies or antagonists of unidentified receptors would be novel therapeutic strategies for several diseases, including obesity, diabetes mellitus, atherosclerosis and cardiovascular disease. Significant roles of FABP4 as a lipid chaperone in physiological and pathophysiological conditions and the possibility of FABP4 being a therapeutic target for metabolic and cardiovascular diseases are discussed in this review.

Ashitaba (Angelica keiskei) Exerts Possible Beneficial Effects on Metabolic Syndrome

Metabolic syndrome is a serious health condition comprising a combination of glucose metabolism disorder, high blood pressure and obesity. The main underlying risk factors for metabolic syndrome are abdominal obesity and insulin resistance. Various studies have shown that herbal medicines can be effective against these aspects of metabolic syndrome. Angelica keiskei Koidzumi (ashitaba) is a large perennial herb that is native to the South East Pacific coast of Japan, and it has recently become popular as a herbal medicine, dietary supplement and health food in Asian countries. Ashitaba leaves, stems and roots contain abundant nutrients and dietary fiber, as well as various natural substances such as chalcones, flavanones and coumarins. Various physiological and biological activities of ashitaba and its natural substances have recently been reported. Although numerous reports describe health benefits of ashitaba, it is most popularly applied against metabolic syndrome. Here, we introduce current information derived from studies on the effects of ashitaba on various pathological disorders associated with metabolic syndrome.

The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis

Metabolic syndrome is characterized by obesity, hyperglycemia, hypertension, insulin resistance, and dyslipidemia. Metabolic syndrome is associated with osteoarthritis (OA), but it is unclear if the association is attributable to increased mechanical loading on joints caused by obesity or other aspects of metabolic syndrome. Here we examined the effects of altered metabolism, obesity, and the gut microbiome on load-induced OA. Cartilage damage was induced through cyclic compressive loading in four groups of adult male mice: Toll-like receptor-5 deficient (TLR5KO) mice that develop metabolic syndrome due to alterations in the gut microbiome, TLR5KO mice submitted to chronic antibiotics to prevent metabolic syndrome (TLR5KOΔMicrobiota), C57BL/6J mice fed a high fat diet to cause obesity (HFD), and untreated C57BL/6J mice (WT). Loading was applied for 2 weeks (n=10-11/group) or 6 weeks (n=10-11/group). After 2 weeks of loading, cartilage damage (OARSI score) was not different among groups. After 6 weeks of loading, HFD mice had increased load-induced cartilage damage, while TLR5KO mice had cartilage damage comparable to WT mice. TLR5KOΔMicrobiota mice had less cartilage damage than other groups. HFD mice had elevated serum inflammatory markers. Each group had a distinct gut microbiome composition. Severe obesity increased load-induced cartilage damage, while milder changes in adiposity/metabolic syndrome seen in TLR5KO mice did not. Furthermore, the effects of systemic inflammation/obesity on cartilage damage depend on the duration of mechanical loading. Lastly, reduced cartilage damage in the TLR5KOΔMicrobiota mice suggests that the gut microbiome may influence cartilage pathology.

Protection of Progression of Nonalcoholic Steatohepatitis in Diet-Induced Obese Mice by a Low-Iron Diet

Iron is a risk factor for type 2 diabetes, but its relationship to other aspects of metabolic syndrome is less clear. To investigate iron’s relation to nonalcoholic steatohepatitis (NASH), mice were fed a “fast food” (FF)-diet (40% energy as fat, 12% SFA, 0.2% cholesterol, and 18.9 g/L glucose and 23.1 g/L fructose in their drinking water) for 10 or 24 weeks. The diets contained either 4 (low iron, LI), 35 (normal iron, NI) or 2000mg iron/kg chow (high iron, HI). HOMA-IR values were 2.2-fold higher (p&amp;lt;0.001) in the FF-groups at 10 weeks, but did not increase further with HI (1.48-fold, p=0.5). At 10 weeks all groups had similar glucose excursions during glucose and pyruvate tolerance testing. There was no significant difference in IP-GTT or IP-PTT area under the glucose curve. Liver triglycerides (TG) were significantly increased by FF (4.2-fold, p&amp;lt;0.01) but not iron at 10 weeks. The effect of FF was greater at 24 weeks (22.4 fold p&amp;lt;0.001), and at 24 weeks iron further increased liver TG (3.3 fold HIFF vs. LIFF, p&amp;lt;0.001). A marker of liver injury (ALT) increased 10.3-fold (p&amp;lt;0.001) on the HIFF diet compared to LI normal chow, but only 3.2-fold (p&amp;lt;0.05) on LIFF. The fibrotic gene collagen1alpha increased 14.3-fold (p&amp;lt;0.001) in HIFF but not at all (0.8-fold) on LIFF compared to LI normal chow. Similar protection was afforded by the LI diet to increases in expression of the inflammatory genes TGF-beta and TNF-alpha seen in HIFF. RNA sequencing data revealed transcriptional regulation of a large family of fat metabolic genes by FF, whereas only the TGF-beta signaling pathway was significantly altered by iron content. We conclude that dietary iron restriction can protect from NASH induced by a high-fat and -carbohydrate diet. A likely candidate mechanism is through a known mediator of hepatic fibrosis, TGF-beta. Disclosure L. Salaye: None. I. Bychkova: None. F. Lorenzo: None. S.T. Sink: None. D. McClain: None.