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Endocrinology AND Hyperlipidemia [keywords]
- Disruption of ldlr causes increased LDL-cholesterol and vascular lipid accumulation in a zebrafish model of hypercholesterolemia. [JOURNAL ARTICLE]
- J Lipid Res 2014 Sep 8.
Hyperlipidemia and arterial cholesterol accumulation are primary causes of cardiovascular events. Monogenic forms of hyperlipidemia and recent GWAS indicate that genetics plays an important role. Zebrafish are a useful model for studying the genetic susceptibility to hyperlipidemia owing to conservation of many components of lipoprotein metabolism - including those related to low density lipoprotein (LDL), ease of genetic manipulation, and in vivo observation of lipid transport and vascular calcification. We sought to develop a genetic model for lipid metabolism in zebrafish, capitalizing on one well-understood player in LDL cholesterol transport, the LDL receptor (ldlr), and an established in vivo model of hypercholesterolemia. We report that morpholinos targeted against the gene encoding ldlr effectively suppressed its expression in embryos during the first 8 days of development. ldlr morphants exhibited increased LDL-cholesterol (LDL-c) levels that were exacerbated by feeding a high cholesterol diet. Increased LDL-c was ameliorated in morphants upon treatment with atorvastatin. Furthermore, we observed significant vascular and liver lipid accumulation, vascular leakage, and plaque oxidation in ldlr-deficient embryos. Finally, upon transcript analysis of several cholesterol-regulating genes we observed changes similar to those seen in mammalian systems, suggesting that cholesterol regulation may be conserved in zebrafish. Taken together, these observations indicate conservation of ldlr function in zebrafish and demonstrate the utility of transient gene knockdown in embryos as a genetic model for hyperlipidemia.
- Variability in myosteatosis and insulin resistance induced by high-fat diet in mouse skeletal muscles. [Journal Article, Research Support, Non-U.S. Gov't]
- Biomed Res Int 2014.:569623.
Nutrient overload leads to impaired muscle oxidative capacity and insulin sensitivity. However, comparative analyses of the effects of dietary manipulation on skeletal muscles with different fiber composition are lacking. This study aimed to investigate the selective adaptations in the soleus and tibialis anterior muscles evoked by administration of high-fat diet for 12 weeks in 10 mice (HFD mice) compared to 10 animals fed with a normal chow diet (control mice). Mice fed with the HFD diet exhibited hyperlipidemia, hyperinsulinemia, hyperglycemia, and lower exercise capacity in comparison to control mice. In control mice, soleus fibers showed higher lipid content than tibialis anterior fibers. In contrast, the lipid content was similar between the two muscles in HFD mice. Significant differences in markers of muscle mitochondrial production and/or activity as well as of lipid synthesis were detected between HFD mice and control mice, especially in the tibialis anterior. Moreover, translocation of GLUT-4 transporter to the plasma membrane and activation of the insulin signaling pathway were markedly inhibited in the tibialis and slightly reduced in the soleus of HFD mice compared to control mice. Overall, these results show that adaptive responses to dietary manipulation occur in a muscle-specific pattern.
- Dietary supplementation with tomato-juice in patients with metabolic syndrome: A suggestion to alleviate detrimental clinical factors. [JOURNAL ARTICLE]
- Food Chem Toxicol 2014 Sep 3.:9-13.
Lycopene, a carotenoid, is known for its antioxidant properties. Little is known, though, about the relationship of dietary tomato-juice intake and risks factors, like inflammation, insulin resistance and hyperlipidemia, implicated in metabolic syndrome. In the present study, we examined whether supplementation with tomato-juice has any implication on the risk status of patients with metabolic syndrome. A comparative study was conducted in 27 individuals diagnosed with metabolic syndrome. Fifteen of them were instructed to use commercially available tomato-juice as refreshment 4 times a week over a period of two months and twelve individuals served as the control group. Several parameters reflective of the metabolic syndrome were monitored both in the group supplemented with tomato juice and in the control group (ADMA for entdothelial function, TNF-α and IL-6 for inflammation, FIRI for insulin resistance). There was a significant improvement in the inflammation status and the endothelial dysfunction of the tomato-juice supplemented patients. At the same time, insulin resistance improved and a pronounced decrease in LDL was recorded, along with a slight increase in HDL. The results of the present study suggest an alleviating effect of tomato-juice with regard to risk factors associated with metabolic syndrome.
- Determinants of VLDL composition and apo B-containing particles in familial combined hyperlipidemia. [JOURNAL ARTICLE]
- Clin Chim Acta 2014 Aug 27.:160-165.
In familial combined hyperlipidemia (FCHL) the severity of the dyslipidemia is determined by an overproduction of VLDL (very low density lipoprotein) particles and by its abnormal lipid composition. However, few are known regarding the metabolic factors that determine these abnormalities. We investigated the impact of metabolic factors on the number of atherogenic particles (apolipoprotein B level (apoB)) and the triglyceride content of very low-density lipoproteins (VLDLs-TG).A cross-sectional study done in FCHL subjects and gender and age-matched healthy subjects. A clinical assessment, lipid profile and plasma concentrations of insulin, apolipoprotein CIII (apo CIII), apolipoprotein AII (apo AII), high sensitive C-reactive protein (HS-CRP), adiponectin and leptin were documented in 147 FCHL patients and 147 age-matched healthy subjects. Multivariate regression models were performed to investigate the independent determinants of VLDL-TG and apo B levels adjusting for confounding factors.The variables that determined the VLDL-triglyceride content as a surrogate of VLDL composition were apo CIII (β=0.365, p<0.001), insulin (β=0.281, p<0.001), Apo AII (β=0.145, p<0.035), and adiponectin levels (β=-0.255, p<0.001). This model explained 34% of VLDL composition (VLDL-TG) variability. However, none of these variables were independent contributors of apo B-containing particles.In patients with FCHL apo CIII, apo AII and adiponectin are major novel factors determining the VLDL particle composition. However, such factors do not explain apo B-containing particles.
- Lowered cutoff points of obesity indicators are better predictors of hypertension and diabetes mellitus in premenopausal Taiwanese women. [JOURNAL ARTICLE]
- Obes Res Clin Pract 2014 Aug 22.
In previous study, we found that in order to prevent MS in women aged <65 years, the cutoff points of obesity indicators should be lowered.To investigate whether our proposed cutoff points of obesity indicators predict the occurrence of hypertension (HT), diabetes mellitus (DM), and hyperlipidemia in premenopausal women with greater sensitivity and specificity compared to reference cutoff points of obesity that are currently being used.Using the database of the "2002 Survey on the Prevalence of Hypertension, Hyperglycemia and Hyperlipidemia in Taiwan" provided by the Bureau of Health Promotion, Taiwan as research material, data from 2270 premenopausal women aged 20-65 years were used for the analyses. The receiver-operating characteristic curves (ROC) of the body-mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were used to predict HT, DM, and hyperlipidemia.Obesity is not a good predictor of the occurrence of hyperlipidemia in premenopausal women aged <65 years. However, our proposed cutoff points had greater sensitivity and specificity than did the reference cutoff points. To prevent the risk of HT and DM in premenopausal women, the cutoff points of obesity indicators should be reduced. The proposed values are as follows: a WHR of 0.79; a WC of 74.7cm; a WHtR of 0.49; and a BMI of 22.3kg/m(2).
- Preliminary study: Evaluation of melatonin secretion in children and adolescents with type 1 diabetes mellitus. [Journal Article]
- Indian J Endocrinol Metab 2014 Jul; 18(4):565-8.
Melatonin is an indolamine hormone, synthesized from tryptophan in the pineal gland primarily. Melatonin exerts both antioxidative and immunoregulatory roles but little is known about melatonin secretion in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to measure serum melatonin levels in patients with T1DM and investigates their relationship with type 1 diabetes mellitus.Forty children and adolescents with T1DM (18 boys and 22 girls) and 30 healthy control subjects (17 boys and 13 girls) participated in the study. All patients followed in Pediatric Endocrinology and Metabolism Unit of Gaziantep University Faculty of Medicine and also control subjects had no hypertension, obesity, hyperlipidemia, anemia, and infection. Blood samples were collected during routine analysis, after overnight fasting. Serum melatonin levels were analyzed with ELISA.There were no statistically significant differences related with age, sex, BMI distribution between diabetic group and control group. Mean diabetic duration was 2.89 ± 2.69 years. The variables were in the equation. Mean melatonin level in diabetic group was 6.75 ± 3.52 pg/ml and mean melatonin level in control group was 11.51 ± 4.74 pg/ml. Melatonin levels were significantly lower in diabetic group compared to controls (P < 0.01).Melatonin was associated with type 1 diabetes mellitus significantly. Because of the varied roles of melatonin in human metabolic rhythms, these results suggest a role of melatonin in maintaining normal rhythmicity. Melatonin may play role in preventing process of inflammation and oxidative stress.
- The association of vitamin D deficiency with non-alcoholic fatty liver disease. [Journal Article]
- Clinics (Sao Paulo) 2014 Aug; 69(8):542-6.
Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease.We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease.The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl).In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.
- Tissue-specific insulin signaling in the regulation of metabolism and aging. [Journal Article]
- IUBMB Life 2014 Jul; 66(7):485-95.
In mammals, insulin signaling regulates glucose homeostasis and plays an essential role in metabolism, organ growth, development, fertility, and lifespan. The defects in this signaling pathway contribute to various metabolic diseases such as type 2 diabetes, polycystic ovarian disease, hypertension, hyperlipidemia, and atherosclerosis. However, reducing the insulin signaling pathway has been found to increase longevity and delay the aging-associated diseases in various animals, ranging from nematodes to mice. These seemly paradoxical findings raise an interesting question as to how modulation of the insulin signaling pathway could be an effective approach to improve metabolism and aging. In this review, we summarize current understanding on tissue-specific functions of insulin signaling in the regulation of metabolism and lifespan. We also discuss the potential benefits and limitations in modulating tissue-specific insulin signaling pathway to improve metabolism and healthspan. © 2014 IUBMB Life, 66(7):485-495, 2014.
- Elevated GH/IGF-I promotes mammary tumors in high-fat, but not low-fat, fed mice. [JOURNAL ARTICLE]
- Carcinogenesis 2014 Aug 1.
GH and/or IGF-I are thought to promote breast cancer based on reports showing circulating IGF-I levels correlate, in epidemiological studies, with breast cancer risk. Also, mouse models with developmental GH/IGF-I deficiency/resistance are less susceptible to genetic- or chemical-induced mammary tumorigenesis. However, given the metabolic properties of GH, medical strategies have been considered to raise GH to improve body composition and metabolic function in elderly and obese patients. Since hyperlipidemia, inflammation, insulin resistance and obesity increase breast cancer risk, elevating GH may serve to exacerbate cancer progression. To better understand the role GH/IGF-I plays in tumor formation, this study used unique mouse models to determine if reducing GH/IGF-I in adults protects against DMBA-induced mammary tumor development, and if moderate elevations in endogenous GH/IGF-I alter DMBA-induced tumorigenesis in mice fed a standard-chow diet or in mice with altered metabolic function due to high-fat feeding. We observed that adult-onset isolated GH deficient (AOiGHD) mice, which also have reduced IGF-I levels, were less susceptible to DMBA-treatment. Specifically, fewer AOiGHD mice developed mammary tumors compared to GH-replete controls. In contrast, chow-fed mice with elevated endogenous GH/IGF-I (HiGH mice) were not more susceptible to DMBA-treatment. However, high-fat-fed, HiGH mice showed reduced tumor latency and increased tumor incidence compared to diet-matched controls. These results further support a role of GH/IGF-I in regulating mammary tumorigenesis but suggest the ultimate consequences of GH/IGF-I on breast tumor development are dependent on the diet and/or metabolic status.
- Glucagon-like peptide 1 receptor agonist is more efficacious than insulin glargine for poorly controlled type 2 diabetes: a systematic review and meta-analysis. [JOURNAL ARTICLE]
- J Diabetes 2014 Jul 21.
To compare the reported efficacy and safety of glucagon-like peptide-l receptor agonist (GLP-1RA) and insulin glargine (IGlar) for poorly controlled type 2 diabetes.Medline, EMBASE, Cochrane Library, and clinicaltrials.gov were carried out. References and cited papers of relevant articles were also checked.Seven trials met the inclusion criteria. GLP-1RA showed equivalent or superior efficacy to IGlar for reducing haemoglobin A1c (HbA1c) , with a greater proportion of patients achieving HbAlc<7%. GLP-1RA also favoured decreased body weight, total cholesterol (TC), low-density lipoprotein (LDL), and systolic blood pressure (SBP). Serious adverse events were uncommon and not significantly different. More patients taking GLP-1RA experienced gastrointestinal complications: nausea, diarrhoea, and vomiting. Severe hypoglycaemia events were rare, and minor hypoglycaemia was less common for GLP-1RA.GLP-1RA showed greater efficacy compared to IGlar for type 2 diabetes, and it may also prove beneficial for other diabetes-associated characteristics, including obesity, hypertension, and hyperlipidaemia.