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Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obesity has been continuously increasing, especially in rural areas of South Korea. Therefore, it is important to examine various genetic, behavioral, and environmental factors associated with obesity in these rural areas. The Korean Society for the Study of Obesity commenced a community-based prospective cohort study of the Gangwon area called the Gangwon Obesity and Metabolic Syndrome (GOMS) study to investigate longitudinal changes in the status of obesity and its related factors. Methods: A total of 317 adults 40-69 years of age were recruited from Hongcheon and Inje districts, Gangwon province, as part of the first wave of this cohort study. Information on participants' demographic, behavioral, psychological, dietary, and environmental factors and past medical histories were collected by self-administered questionnaires and interviewer-administered questionnaires. Anthropometric measurements, blood tests, and a hand grip strength test were performed, and skin keratin and stool samples were collected. Among the 317 enrolled subjects, two participants who did not have anthropometric data were excluded from the data analyses, resulting in an inclusion of a total of 315 participants. Results: The mean age of the 315 participants in the GOMS initial baseline survey was 58.5 years old, 87 of them were men, and the mean body mass index was 24.7±3.7 kg/m2. Among all participants, 48.9% had hypertension, 21.4% had diabetes mellitus (DM), 55.6% had dyslipidemia, and 46.0% had metabolic syndrome (MS). Both the prevalence rates of DM and MS were significantly higher in men. Conclusion: The first baseline survey of the GOMS study was initiated, and a more detailed analysis of respondents' data is expected to be continued. Further follow-up and additional recruitment will allow the investigation of risk factors and the etiology of obesity and its comorbidities in rural areas of Gangwon province. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. Methods: This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. Results: In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes. Conclusion: The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Objective To determine whether the bioimpedance analysis (BIA) ratios of upper to lower extremities could predict treatment outcomes after complex decongestive therapy (CDT) for gynecological cancer related lymphedema (GCRL). Methods A retrospective study, from March 2015 to December 2018, was conducted. The study sample comprised patients receiving CDT, 30 minutes per day, for 10 days. Bioimpedance was measured pre- and post-CDT. Circumference measurements were obtained at 20 and 10 cm above the knee (AK) and 10 cm below the knee (BK). We calculated the expected impedance at 0 Hz (R0) of extremities and upper/lower extremity R0 ratios (R0U/L). We evaluated the relationship between R0U/L and changes in R0U/L and circumferences, pre- and post-CDT. Results Overall, 59 patients were included in this study. Thirty-one lower extremities in 26 patients comprised the acute group, and 38 lower extremities in 33 patients comprised the chronic group. Pre-treatment R0U/L was significantly correlated with R0U/L change after adjusting for age and BMI (acute: R=0.513, p<0.01; chronic: R=0.423, p<0.01). In the acute group, pre-treatment R0U/L showed a tendency to be correlated with circumference change (AK 20 cm: R=0.427, p=0.02; AK 10 cm: R=0.399, p=0.03). Conclusion Our study results suggested that pre-treatment BIA could predict volume reductions after CDT in the early stages of GCRL. These findings implied that BIA value could be one possible parameter to apply in treatment outcomes prediction, during the early stage of GCRL. Therefore, further large-scale prospective studies will be beneficial. [ABSTRACT FROM AUTHOR]

Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) =35 kg/m². Agreeing with the International Federation for the Surgery of Obesity and Metabolic Disorders, Asian Pacific Chapter consensus, we determined that bariatric surgery is indicated for Korean patients with BMI =35 kg/m² and for Korean patients with BMI =30 kg/m² who have comorbidities. The new guidelines focus on guiding clinicians and patients to manage obesity more effectively. Our recommendations and treatment algorithms can serve as a guide for the evaluation, prevention, and management of overweight and obesity. [ABSTRACT FROM AUTHOR]

Malonyl-CoA is an important central metabolite for the production of diverse valuable chemicals including natural products, but its intracellular availability is often limited due to the competition with essential cellular metabolism. Several malonyl-CoA biosensors have been developed for high-throughput screening of targets increasing the malonyl-CoA pool. However, they are limited for use only in Escherichia coli and Saccharomyces cerevisiae and require multiple signal transduction steps. Here we report development of a colorimetric malonyl-CoA biosensor applicable in three industrially important bacteria: E. coli, Pseudomonas putida, and Corynebacterium glutamicum. RppA, a type III polyketide synthase producing red-colored flaviolin, was repurposed as a malonyl-CoA biosensor in E. coli. Strains with enhanced malonyl-CoA accumulation were identifiable by the colorimetric screening of cells showing increased red color. Other type III polyketide synthases could also be repurposed as malonyl-CoA biosensors. For target screening, a 1,858 synthetic small regulatory RNA library was constructed and applied to find 14 knockdown gene targets that generally enhanced malonyl-CoA level in E. coli. These knockdown targets were applied to produce two polyketide (6-methylsalicylic acid and aloesone) and two phenylpropanoid (resveratrol and naringenin) compounds. Knocking down these genes alone or in combination, and also in multiple different E. coli strains for two polyketide cases, allowed rapid development of engineered strains capable of enhanced production of 6-methylsalicylic acid, aloesone, resveratrol, and naringenin to 440.3, 30.9, 51.8, and 103.8 mg/L, respectively. The malonyl-CoA biosensor developed here is a simple tool generally applicable to metabolic engineering of microorganisms to achieve enhanced production of malonyl-CoA-derived chemicals. [ABSTRACT FROM AUTHOR]

Background: Growing evidence for clinically significant differences between the sexes has attracted the attention of researchers. However, failures to report a test animal sex and balance the sex ratios of study samples remain widespread in preclinical investigations. We analyzed the sex-reporting rate and sex distributions of test animals in published oncology studies. Methods: We selected five oncology journals included in the Scientific Citation Index (SCI) based on impact factors. We identified preclinical investigations with in vivo mouse experiments published in 2015 for inclusion in our study sample. We classified each article by whether or not it reported test subject sex, and by which sex was included. We also recorded whether there were justifications for using one particular sex in single-sex studies (e.g., anatomical reasons) and whether sex-based analyses were conducted for both-sex studies. Results: We surveyed a total of 382 articles. Half (50.3%) failed to report test animal sex. Among articles that did report sex, 91.7% were single-sex studies, of which 69.4% did not provide any justifications for using the sex included in the study. Relatively few studies 15.7 studies included animals of both sexes, and only 2.3 studies conducted sex-based analyses. These findings are consistent with those of previous research that used other methods to collect data from the literature such as text mining, but our analysis of the provision of justifications for using one sex versus the other is a novel feature. Conclusions: Many researchers overlook test subject sex as a factor, but test animal sex should be reported in all preclinical investigations to enhance the reproducibility of research and avoid faulty conclusions drawn from one-sided studies. [ABSTRACT FROM AUTHOR]

Background: We evaluated the clinical characteristics of insulin resistance and β-cell dysfunction in newly diagnosed, drug-naive people with type 2 diabetes by analyzing nationwide cross-sectional data. Methods: We collected the clinical data of 912 participants with newly diagnosed diabetes from 83 primary care clinics and hospitals nationwide from 2015 to 2016. The presence of insulin resistance and β-cell dysfunction was defined as a homeostatic model assessment of insulin resistance (HOMA-IR) value ≥2.5 and fasting C-peptide levels <1.70 ng/mL, respectively. Results: A total of 75.1% and 22.6% of participants had insulin resistance and β-cell dysfunction, respectively. The proportion of participants with insulin resistance but no β-cell dysfunction increased, and the proportion of participants with β-cell dysfunction but no insulin resistance decreased as body mass index (BMI) increased. People diagnosed with diabetes before 40 years of age had significantly higher HOMA-IR and BMI than those diagnosed over 65 years of age (HOMA-IR, 5.0 vs. 3.0; BMI, 28.7 kg/m² vs. 25.1 kg/m²). However, the β-cell function indices were lower in people diagnosed before 40 years of age than in those diagnosed after 65 years of age (homeostatic model assessment of β-cell function, 39.3 vs. 64.9; insulinogenic index, 10.3 vs. 18.7; disposition index, 0.15 vs. 0.25). Conclusion: We observed that the main pathogenic mechanism of type 2 diabetes is insulin resistance in participants with newly diagnosed type 2 diabetes. In addition, young adults with diabetes are more likely to have higher insulin resistance with obesity and have higher insulin secretory defect with severe hyperglycemia in the early period of diabetes than older populations. [ABSTRACT FROM AUTHOR]

Aromatic polyesters are widely used plastics currently produced from petroleum. Here we engineer Escherichia coli strains for the production of aromatic polyesters from glucose by one-step fermentation. When the Clostridium difficile isocaprenoyl-CoA:2-hydroxyisocaproate CoA-transferase (HadA) and evolved polyhydroxyalkanoate (PHA) synthase genes are overexpressed in a D-phenyllactate-producing strain, poly(52.3 mol% 3-hydroxybutyrate (3HB)-co-47.7 mol% D-phenyllactate) can be produced from glucose and sodium 3HB. Also, various poly(3HB-co-D-phenyllactate) polymers having 11.0, 15.8, 20.0, 70.8, and 84.5 mol% of D-phenyllactate are produced from glucose as a sole carbon source by additional expression of Ralstonia eutropha β-ketothiolase (phaA) and reductase (phaB) genes. Fed-batch culture of this engineered strain produces 13.9 g l-1 of poly(61.9 mol% 3HB-co-38.1 mol% Dphenyllactate). Furthermore, different aromatic polyesters containing D-mandelate and D-3- hydroxy-3-phenylpropionate are produced from glucose when feeding the corresponding monomers. The engineered bacterial system will be useful for one-step fermentative production of aromatic polyesters from renewable resources. [ABSTRACT FROM AUTHOR]

This paper aimed to evaluate the applicability of adiabatic humidification in the heating, ventilation, and air conditioning (HVAC) systems of semiconductor cleanrooms. Accurate temperature and humidity control are essential in semiconductor cleanrooms and high energy consumption steam humidification is commonly used. Therefore, we propose an adiabatic humidification system employing a pressurized water atomizer to reduce the energy consumption. The annual energy consumption of three different HVAC systems were analyzed to evaluate the applicability of adiabatic humidification. The studied cases were as follows: (1) CASE 1: a make-up air unit (MAU) with a steam humidifier, a dry cooling coil (DCC), and a fan filter unit (FFU); (2) CASE 2: a MAU with the pressurized water atomizer, a DCC, and a FFU; and (3) CASE 3: a MAU, a DCC, and a FFU, and the pressurized water atomizer installed in the return duct. The energy saving potential of adiabatic humidification over steam humidification has been proved, with savings of 8% and 23% in CASE 2 and CASE 3 compared to CASE 1, respectively. Furthermore, the pressurized water atomizer installed in the return duct exhibits greater energy saving effect than when installed in the MAU. [ABSTRACT FROM AUTHOR]

Background: We aimed to study the importance of diabetes education by investigating diabetes education rate and the associations between the presence/absence of diabetes education and the clinical outcomes of diabetic patients in Korea. Methods: In the Fifth Korea National Health and Nutrition Examination survey (KNHANES V), a cross-sectional national survey during 2010 and 2012, 1498 subjects aged over 30 years and older were diagnosed with diabetes by doctors. The subjects were analyzed by a complex samples model. Results: Only 20.3% of diabetes patients received diabetes education, and this was not significantly different between age groups. Education was delivered in hospitals/clinics, public health centers, and public lectures (15.7%, 3.0% and 1.4%, respectively). After adjusting for age, sex, and duration of diabetes, the factors independently associated with the presence of diabetes education were higher education level, frequent walking habit, and parameters regarding the presence of dyslipidemia, insulin treatment, and non-pharmacologic treatment. Among continuous variables, only the duration of diabetes was associated with diabetes education status; metabolic parameters were not associated with diabetes education status. Conclusion: Diabetes is a chronic disease and education on diabetes is very important. The education rate was low and quality of the education is doubtful. An effort to raise the rate of diabetes education and further study to raise the quality of diabetes training are necessary. [ABSTRACT FROM AUTHOR]

Adiponectin and tumor necrosis factor-α (TNF-α) exert opposite effects on obesity-associated inflammation and insulin signaling. The purpose of the present study was to investigate the effects of chronic TNF-α on adiponectin levels in 3T3-L1 adipocytes, as well as the potential reversal mechanisms. Differentiated 3T3-L1 adipocytes were exposed to TNF-α for three different incubation times and then to various wash-off periods with or without mitogen-activated protein kinase (MAPK) inhibitors. TNF-α significantly reduced adiponectin gene expression in a dose- and time-dependent manner and activated c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and p38 MAPK. A 16 h restoration period fully reversed the decrease in adiponectin levels following 16 h treatment with TNF-α; however, 16 h withdrawal of TNF-α following 32 or 48 h treatment did not completely reverse the TNF-α-induced decrease in adiponectin levels. In 3T3-L1 adipocytes, 32 or 48 h wash-off periods were required following 32 or 48 h TNF-α treatments, respectively. The pattern of ERK activation following TNF-α exposure and removal was similar to the pattern of adiponectin expression. Furthermore, ERK1/2 inhibition accelerated the recovery of adiponectin levels compared with the levels in the untreated control adipocytes. Therefore, the inhibitory effects of TNF-α on adiponectin levels in differentiated 3T3-L1 cells were fully reversed following a wash-out period equivalent to the TNF-α treatment time, potentially through the ERK 1/2 pathway. [ABSTRACT FROM AUTHOR]

Multilayer graphene is synthesized by a simplified process employing an evaporator in which a target substrate is deposited with a Ni catalyst layer before being heated to grow graphene directly. Carbon atoms adsorbed onto the surface of the Ni source as impurities from the atmosphere are incorporated into the catalyst layer during the deposition, and diffuse toward the catalyst=substrate interface, where they crystallize as graphene with a thickness of less than 2 nm. The need for a transfer process and external carbon supply is eliminated. The graphene is characterized by conventional analysis approaches, including nano-scale visualization and Raman spectroscopy, and utilizing photonics, graphene-functionalized passive laser mode-locking is demonstrated to confirm the successful synthesis of the graphene layer, resulting in an operating center wavelength of 1569.4 nm, a pulse duration of 1.35 ps, and a repetition rate of 31.6 MHz. [ABSTRACT FROM AUTHOR]

Objective: Angiotensin-converting enzyme 2 (ACE2) plays an important role in glucose metabolism and renal function. However, the relationship between ACE2 and hyperglycemia or microalbuminuria has not been established in humans. We investigated whether urinary ACE2 levels are associated with abnormal glucose homeostasis and urinary albumin excretion. Methods: We developed an ELISA for quantifying ACE2 in urine. The ELISA was used to measure urinary ACE2 levels in 621 subjects with: normal glucose tolerance (NGT; n=77); impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n=132); and type 2 diabetes mellitus (T2DM, n=412). Insulin resistance was assessed by homeostasis model assessment for insulin resistance (HOMA-IR) index and urinary albumin excretion by urine albumin-to-creatinine ratio (ACR). Other biochemical and anthropometric parameters were measured. Results: Urinary ACE2 levels were significantly higher in insulin-resistant subjects with IFG, IGT, and T2DM than in the NGT group (P<0.001). Urinary ACE2 concentrations appeared to correlate with HOMA-IR, fasting blood glucose, triglyceride, high-sensitivity C-reactive protein, serum creatinine, urinary ACR, and systolic blood pressure (all P<0.05). After adjustment for impaired renal function and other metabolic parameters, urinary ACE2 concentration was still associated with a higher risk for T2DM (OR 1.80, 95% CI 1.05-3.08, P=0.02). In addition, urinary ACE2 levels were highly predictive of microalbuminuria after adjusting for clinical risk factors (OR 2.68, 95% CI 1.55-4.64, P<0.001). Conclusion: Our data suggest that the urinary ACE2 level is closely associated with T2DM and is an independent risk factor for microalbuminuria. [ABSTRACT FROM AUTHOR]

Long-range air travel or 24-hour working service has increased the risk of exposure to the jet-lag or the shift-lag by disturbing the circadian timing system. Recently, diabetes is becoming epidemic worldwide and many diabetic patients are prone to be long-range air travellers or shift workers. A lifestyle change resulting in disruption of light-dark cycle could make suprachiasmatic nucleus in which circadian clock is believed to reside vulnerable to dysregulation of circadian rhythm and adverse effects on body homeostasis. Unfortunately, misalignment of circadian rhythm ocurred in air travelers and shift workers have been known to be associated with hormonal dysregulation and various health problems such as psychosocial, cardiometabolic and malignant disease. Here, we review the effect of diurnal change in the circadian timing system on the human body homeostasis, symptom and disease. Also, we discuss the risk of diabetes under irregular circadian rhythm and track proper management for air travelers with diabetes. [ABSTRACT FROM AUTHOR]

Objective To evaluate the prevalence of and risk factors for diabetic retinopathy (DR) in Koreans with type II diabetes. Methods Subjects (400 male, 296 female) aged 30e65 years (mean 55.3 years) with hyperglycaemia (fasting plasma glucose $7.0 mmol/ml) or known diabetes (mean6SD duration 6.3665.73 years) were enrolled in the Seoul Metro-City Diabetes Prevention Program (SMC-DPP) from September 2008 to September 2009. The severity of DR was diagnosed by grading fundus photographs taken from five standard fields per eye and categorised following the Early Treatment of Diabetic Retinopathy Study grading protocol. All participants underwent routine clinical and laboratory examinations to evaluate risk factors for DR. Results The overall prevalence of any type of DR was 18.7%. Logistic regression analyses showed that the following factors were significantly associated with DR after adjustment for age and gender, duration of diabetes, serum glycated haemoglobin A1c (HbA1c), mean arterial pressure, serum total cholesterol and serum triglycerides: duration of diabetes (OR 1.14, 95% CI 1.10 to 1.18, for 1 year increase), HbA1c (OR 1.49, 95% CI 1.20 to 1.85, for 1% increase), serum concentration of insulin (OR 0.87, 95% CI 0.81 to 0.94, for 1 mIU/ml increase), homoeostasis model assessment of insulin resistance (OR 0.06, 95% CI 0.01 to 0.29, for 10 unit increase), and presence of macroalbuminuria (OR 5.14, 95% CI 1.45 to 18.20, albumin to creatinine ratio >300 mg/g). Conclusions In addition to traditional risk factors, insulin resistance was associated with an increased risk of DR in Koreans with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: In order to reduce time and efforts to develop microbial strains with better capability of producing desired bioproducts, genome-scale metabolic simulations have proven useful in identifying gene knockout and amplification targets. Constraints-based flux analysis has successfully been employed for such simulation, but is limited in its ability to properly describe the complex nature of biological systems. Gene knockout simulations are relatively straightforward to implement, simply by constraining the flux values of the target reaction to zero, but the identification of reliable gene amplification targets is rather difficult. Here, we report a new algorithm which incorporates physiological data into a model to improve the model's prediction capabilities and to capitalize on the relationships between genes and metabolic fluxes. Results: We developed an algorithm, flux variability scanning based on enforced objective flux (FVSEOF) with grouping reaction (GR) constraints, in an effort to identify gene amplification targets by considering reactions that co-carry flux values based on physiological omics data via "GR constraints". This method scans changes in the variabilities of metabolic fluxes in response to an artificially enforced objective flux of product formation. The gene amplification targets predicted using this method were validated by comparing the predicted effects with the previous experimental results obtained for the production of shikimic acid and putrescine in Escherichia coli. Moreover, new gene amplification targets for further enhancing putrescine production were validated through experiments involving the overexpression of each identified targeted gene under condition-controlled batch cultivation. Conclusions: FVSEOF with GR constraints allows identification of gene amplification targets for metabolic engineering of microbial strains in order to enhance the production of desired bioproducts. The algorithm was validated through the experiments on the enhanced production of putrescine in E. coli, in addition to the comparison with the previously reported experimental data. The FVSEOF strategy with GR constraints will be generally useful for developing industrially important microbial strains having enhanced capabilities of producing chemicals of interest. [ABSTRACT FROM AUTHOR]

Hypertension and arterial stiffness are associated with an increasing risk of diabetes and cardiovascular diseases. This study aimed to identify genetic variants affecting hypertension and arterial stiffness in diabetic subjects and to compare genetic associations with hypertension between prediabetic and diabetic subjects. A total of 1,069 participants (326 prediabetic and 743 diabetic subjects) were assessed to determine the genetic variants affecting hypertension by analyzing 52 SNPs previously reported to be associated with hypertension. Moreover, the SNPs were tested for association with hemodynamic parameters related to hypertension. Out of the 52 SNPs analyzed, four SNPs including rs5326 (DRD1), rs1004467 (CYP17A1), rs2960306 (GRK4), and rs1 1191548 (near NT5C2) in diabetic subjects and rs1530440 (C10orf107) in prediabetic subjects showed a modest association with hypertension (P = 0.0265, 0.0020, 0.0066, 0.0078, and 0.0015, resp; all were insignificant after Bonferroni correction). Of these SNPs, rs1004467 in CYP17A1 was significantly associated with augmentation index in diabetic subjects who were not taking antihypertensive medication (P = 0.0001; corrected P = 0.006) but not in diabetic subjects receiving antihypertensive medication. This finding suggests that certain genetic variations found in diabetic subjects may confer arterial stiffness and the development of hypertension and also be affected by antihypertensive medication. [ABSTRACT FROM AUTHOR]

Background: Sirt6 has been implicated in the regulation of hepatic lipid metabolism and the development of hepatic steatosis. The aim of this study was to address the potential role of Sirt6 in the protective effects of rosiglitazone (RGZ) on hepatic steatosis. Methods: To investigate the effect of RGZ on hepatic steatosis, rats were treated with RGZ (4 mg·kg-1·day-1) by stomach gavage for 6 weeks. The involvement of Sirt6 in the RGZ's regulation was evaluated by Sirt6 knockdown in AML12 mouse hepatocytes. Results: RGZ treatment ameliorated hepatic lipid accumulation and increased expression of Sirt6, peroxisome proliferatoractivated receptor gamma coactivtor-1-α (Ppargc1a/PGC1-α) and Forkhead box O1 (Foxo1) in rat livers. AMP-activated protein kinase (AMPK) phosphorylation was also increased by RGZ, accompanied by alterations in phosphorylation of LKB1. Interestingly, in free fatty acid-treated cells, Sirt6 knockdown increased hepatocyte lipid accumulation measured as increased triglyceride contents (p = 0.035), suggesting that Sirt6 may be beneficial in reducing hepatic fat accumulation. In addition, Sirt6 knockdown abolished the effects of RGZ on hepatocyte fat accumulation, mRNA and protein expression of Ppargc1a/PGC1-α and Foxo1, and phosphorylation levels of LKB1 and AMPK, suggesting that Sirt6 is involved in RGZmediated metabolic effects. Conclusion: Our results demonstrate that RGZ significantly decreased hepatic lipid accumulation, and that this process appeared to be mediated by the activation of the Sirt6-AMPK pathway. We propose Sirt6 as a possible therapeutic target for hepatic steatosis. [ABSTRACT FROM AUTHOR]