Obesity is a leading risk factor for insulin resistance, hypertension, hyperlipidemia, and cardiovascular complications, collectively referred to as metabolic diseases. Given the prevalence of obesity and its associated medical problems, new strategies are required to prevent or treat obesity and obesity-related metabolic effects. Here we summarize contributors of obesity, and molecular mechanisms controlling adipogenesis from studies in mammalian systems. We also discuss the possibilities of using Drosophila as a genetic model system to advance our understanding of players in fat biology.
Animals ; Drosophila/*physiology ; Humans ; Metabolic Syndrome X/*etiology/metabolism/prevention & control ; Obesity/*complications/metabolism/prevention & control ; PPAR gamma/metabolism/physiology

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is commonly associated with obesity. The spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Fructose ingestion, visceral obesity, and metabolic syndrome are risk factors for liver fibrosis. NAFLD is characterized by two steps of liver injury: intrahepatic lipid accumulation in the setting of insulin resistance, and inflammatory progression to NASH by oxidative stress and inflammatory mediators. Noninvasive methods (e.g., abdominal ultrasonography) are safe ways to support a diagnosis of hepatic steatosis, but liver biopsy remains the gold standard for accurate diagnosis and staging of NASH. Pediatric NASH often displays a histologic pattern distinct from that found in adults. Lifestyle modification through diet and exercise should be attempted in patients diagnosed with NAFLD.
Diet ; Fatty Liver/*diagnosis/therapy/ultrasonography ; Humans ; Inflammation Mediators/metabolism ; Insulin Resistance ; Lipase/genetics ; Membrane Proteins/genetics ; Metabolic Syndrome X/complications ; Reactive Oxygen Species/metabolism ; Risk Factors

No abstract available.
Aged ; Fatty Liver/epidemiology/*etiology/pathology ; Female ; Hepatitis/epidemiology/*etiology/pathology ; Humans ; Insulin Resistance ; Metabolic Syndrome X/*complications/metabolism ; Prevalence ; Prognosis ; Risk Factors

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies that MetS contributes to the development and progression of Alzheimer's disease (AD); however, the factors connecting this association have not been determined. Insulin resistance (IR) is at the core of MetS and likely represent the key link between MetS and AD. In the central nervous system, insulin plays key roles in learning and memory, and AD patients exhibit impaired insulin signaling that is similar to that observed in MetS. As we face an alarming increase in obesity and T2D in all age groups, understanding the relationship between MetS and AD is vital for the identification of potential therapeutic targets. Recently, several diabetes therapies that enhance insulin signaling are being tested for a potential therapeutic benefit in AD and dementia. In this review, we will discuss MetS as a risk factor for AD, focusing on IR and the recent progress and future directions of insulin-based therapies.
Alzheimer Disease/etiology/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Brain/metabolism ; Cognition Disorders/*etiology/*metabolism ; Humans ; Insulin/metabolism ; *Insulin Resistance ; Metabolic Syndrome X/complications/drug therapy/*metabolism ; Molecular Targeted Therapy ; Signal Transduction/drug effects ; tau Proteins/metabolism

OBJECTIVES: This study was performed to investigate the associations between the metabolic syndrome (MetS) and inflammatory markers. METHODS: This cross-sectional analysis was performed using data from 1578 Koreans aged 40-69 years residing in a rural area. We investigated associations between MetS and circulating high sensitivity C-reactive protein (hs-CRP), white blood cells (WBC) and adiponectin. MetS was defined using the criteria proposed by the National Cholesterol Education Program Adult Treatment Panel III (ATP-III). RESULTS: Increased WBC counts and hs-CRP levels and decreased adiponectin levels were observed in subjects with MetS. WBC, hs-CRP and adiponectin levels linearly deteriorated with an increase in the number of MetS components (all ptrend <0.005). Finally, adjusted odds ratios (ORs) for the risk of MetS by increase/decrease in 3 inflammatory markers were calculated by multivariate logistic regression analyses. In terms of changes in inflammation markers, in men, the adjusted ORs (95% confidence interval) were 1.15 (1.01-1.31) for WBC, 1.64 (1.02-2.64) for hs-CRP, and 0.19 (0.08-0.45) for adiponectin, whereas corresponding adjusted ORs (95% CIs) in women were 1.27 (1.15-1.40), 0.98 (0.67-1.42), 0.09 (0.04-0.18), respectively. CONCLUSIONS: Serum adiponectin levels and WBC counts were found to be strongly associated with MetS in both sexes. However, hs-CRP lost its significance after adjusting for BMI and other inflammatory markers in women. This study shows that inflammatory response is associated with MetS in the Korean population. Further prospective studies are necessary to confirm the contribution made by inflammatory markers to the development of MetS.
Adiponectin/blood ; Adult ; Aged ; Biological Markers/blood ; Body Mass Index ; C-Reactive Protein/metabolism ; Female ; Humans ; Inflammation/*blood/complications ; Korea ; Male ; Metabolic Syndrome X/*immunology ; Middle Aged ; Multivariate Analysis ; Rural Population

PURPOSE: Recent studies have revealed close relationships between hepatic injury, metabolic pathways, and gut microbiota. The microorganisms in the intestine also cause irritable bowel syndrome (IBS). The aim of this study was to examine whether IBS was associated with elevated hepatic enzyme [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], gamma-glutamyl transferase (gamma-GT) levels, and metabolic syndrome (MS). MATERIALS AND METHODS: This was a retrospective, cross-sectional, case-control study. The case and control groups comprised subjects who visited our health promotion center for general check-ups from June 2010 to December 2010. Of the 1127 initially screened subjects, 83 had IBS according to the Rome III criteria. The control group consisted of 260 age- and sex-matched subjects without IBS who visited our health promotion center during the same period. RESULTS: Compared to control subjects, patients with IBS showed significantly higher values of anthropometric parameters (body mass index, waist circumference), liver enzymes, gamma-GT, and lipid levels. The prevalences of elevated ALT (16.9% vs. 7.7%; p=0.015) and gamma-GT (24.1% vs. 11.5%; p=0.037) levels were significantly higher in patients with IBS than in control subjects. A statistically significant difference was observed in the prevalence of MS between controls and IBS patients (12.7% vs. 32.5%; p<0.001). The relationships between elevated ALT levels, MS, and IBS remained statistically significant after controlling for potential confounding factors. CONCLUSION: On the basis of our study results, IBS may be an important condition in certain patients with elevated ALT levels and MS.
Adult ; Alanine Transaminase/analysis/*metabolism ; Aspartate Aminotransferases/analysis/*metabolism ; Body Mass Index ; Case-Control Studies ; Cross-Sectional Studies ; Female ; Humans ; Irritable Bowel Syndrome/diagnosis/*enzymology/epidemiology ; Liver/metabolism ; Male ; Metabolic Syndrome X/complications/diagnosis/*enzymology/epidemiology ; Middle Aged ; Obesity/epidemiology ; Prevalence ; Retrospective Studies ; Waist Circumference ; gamma-Glutamyltransferase/analysis/*metabolism

OBJECTIVE: To compare the efficacy of metformin plus megestrol acetate (MA) with that of MA alone for treating endometrial atypical hyperplasia (EAH). METHODS: This pilot study included 16 EAH patients who met at least one metabolic syndrome (MS) criterion and received either adjunctive metformin plus MA (MET group) or MA monotherapy (MA group). Each patient in the MA group received 160 mg of MA daily, whereas patients in the MET group received the same dose of MA plus 0.5 g of metformin thrice daily. Treatment response was assessed by histological examination of dilation and curettage specimens obtained after 12 weeks of therapy. RESULTS: Each group had eight patients, and half of the patients in each group were diagnosed with MS. The complete response (CR) rate was 75% (6/8) in the MET group and 25% (2/8) in the MA group (p=0.105). Complications of MS did not affect the response rates in either group. In the MET group, 75% (3/4) of the patients had CR in the presence or absence of MS. In the MA group, 50% (2/4) of the patients with MS had CR, whereas no patient without MS had CR. No irreversible toxicities were observed. CONCLUSION: Metformin plus MA may be a potential alternative therapy for treating EAH, and the MS status of patients may have no effect on the efficacy of metformin plus MA therapy.
Adult ; Antineoplastic Agents, Hormonal/*therapeutic use ; Drug Therapy, Combination ; Endometrial Hyperplasia/complications/*drug therapy/metabolism ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Megestrol Acetate/*therapeutic use ; Metabolic Syndrome X/complications/metabolism ; Metformin/*therapeutic use ; Pilot Projects ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Single-Blind Method ; Treatment Outcome

BACKGROUND/AIMS: This multicenter, open-labeled, randomized trial was performed to compare the effects of rosuvastatin 10 mg and atorvastatin 10 mg on lipid and glycemic control in Korean patients with nondiabetic metabolic syndrome. METHODS: In total, 351 patients who met the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) levels > or = 130 mg/dL were randomized to receive either rosuvastatin 10 mg (n = 173) or atorvastatin 10 mg (n = 178) for over 6 weeks. RESULTS: After 6 weeks of treatment, greater reductions in total cholesterol (- 35.94 +/- 11.38 vs. - 30.07 +/- 10.46%, p < 0.001), LDL-C (48.04 +/- 14.45 vs. 39.52 +/- 14.42%, p < 0.001), non-high-density lipoprotein cholesterol (- 42.93 +/- 13.15 vs. - 35.52 +/- 11.76%, p < 0.001), and apolipoprotein-B (- 38.7 +/- 18.85 vs. - 32.57 +/- 17.56%, p = 0.002) levels were observed in the rosuvastatin group as compared to the atorvastatin group. Overall, the percentage of patients attaining the NCEP ATP III goal was higher with rosuvastatin as compared to atorvastatin (87.64 vs. 69.88%, p < 0.001). Changes in glucose and insulin levels, and homeostasis model assessment of insulin resistance index were not significantly different between the two groups. The safety and tolerability of the two agents were similar. CONCLUSIONS: Rosuvastatin 10 mg was more effective than atorvastatin 10 mg in achieving NCEP ATP III LDL-C goals in patients with nondiabetic metabolic syndrome, especially in those with lower NCEP ATP III target level goals.
Blood Glucose/metabolism ; Cholesterol, LDL/blood ; Female ; Fluorobenzenes/*administration & dosage ; Hemoglobin A, Glycosylated/metabolism ; Heptanoic Acids/*administration & dosage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage ; Hypercholesterolemia/blood/complications/*drug therapy ; Hyperglycemia/blood/complications/*drug therapy ; Insulin/blood ; Male ; Metabolic Syndrome X/blood/complications/*drug therapy ; Middle Aged ; Pyrimidines/*administration & dosage ; Pyrroles/*administration & dosage ; Sulfonamides/*administration & dosage ; Treatment Outcome

The aim of this study was done to assess the association of lung function with insulin resistance (IR), systemic inflammation, and metabolic syndrome (MetS). In 9,581 apparently healthy non-smoking male adults, pulmonary function, fasting glucose, insulin, lipid profiles and serum high-sensitivity C-reactive protein (hs-CRP) levels were measured, and homeostatic model assessment (HOMA) was used to assess IR. The presence of MetS was defined according to the AHA/NHLBI criteria. The prevalence of MetS was 19.3%. The odds ratio of MetS for restrictive ventilatory pattern was 1.55 (95% confidence interval, 1.12-2.14), and that for obstructive ventilatory pattern was 1.39 (0.66-2.94) after adjustment for confounders. When subjects were divided in 4 groups according to quartiles of FVC or FEV1 (% predicted [pred]), HOMA-IR significantly increased as the FVC or FEV1 (% predicted [pred]) decreased. Individuals in the lowest FVC or FEV1 quartile had the highest hs-CRP level. Prevalence of MetS increased as FVC or FEV1 (% predicted [pred]) quartiles decreased. The abdominal obesity, hs-CRP and HOMA-IR were the independent predictors for the lowest FVC and FEV1 (% predicted [pred]) even after adjustment for confounders. These results indicate that MetS, IR, and systemic inflammation are important risk factors for reduced lung function in nonsmoking Korean males.
Adult ; C-Reactive Protein/analysis ; Forced Expiratory Volume/physiology ; Glucose/metabolism ; Humans ; Inflammation/complications/*physiopathology ; Insulin/blood ; *Insulin Resistance ; Male ; Metabolic Syndrome X/complications/*physiopathology ; Middle Aged ; Obesity/complications ; Odds Ratio ; Pulmonary Ventilation/*physiology ; Republic of Korea ; Respiratory Function Tests ; Risk Factors ; Vital Capacity/physiology

PURPOSE: In the present study, we tested whether the presence of metabolic syndrome (MetS) would worsen the features of inflammation, plasma omega 3 fatty acid levels and antioxidant potential in treated hypertensive patients. MATERIALS AND METHODS: Two groups were classified by the components of MetS: a reference group of treated hypertensive subjects: hypertension (HTN) group (n = 39) and with more than two additional MetS components: HTN with Mets group (n = 40). We further compared the parameters between HTN group and HTN with MetS group. RESULTS: The results showed that age (p < 0.001) and body mass index (BMI) (p < 0.001) were significantly different between HTN group and HTN with MetS group. Age- and BMI-adjusted total radical trapping antioxidant potential (TRAP) (p < 0.01) was significantly lower, whereas age- and BMI-adjusted CD (p < 0.05) and interleukin (IL) 6 (p < 0.05) were significantly higher in HTN with MetS group than in HTN group. Moreover, HTN with MetS group had significantly lower levels of age- and BMI-adjusted plasma phospholipid eicosapentaenoic acid (EPA) than HTN group (p < 0.05). On the other hand, the levels of age- and BMI-adjusted intracellular cell adhesion molecule-1 (ICAM-1), adiponectin and high molecular weight (HMW)-adiponectin were not significantly different between the groups. CONCLUSION: In conclusion, our results showed increased inflammatory marker, reduced antioxidant potential and EPA levels in treated hypertensive patients in the presence of MetS, suggesting the importance of changes of therapeutic lifestyle to modify the features of MetS.
Adiponectin/blood ; Age Factors ; Antihypertensive Agents/therapeutic use ; Antioxidants/*metabolism ; Body Mass Index ; Eicosapentaenoic Acid/*blood ; Female ; Humans ; Hypertension/*blood/drug therapy/*immunology ; Inflammation/*immunology ; Intercellular Adhesion Molecule-1/blood ; Interleukin-6/blood ; Male ; Metabolic Syndrome X/blood/*complications/immunology ; Middle Aged