The hedonic overdrive model best explains high-fat diet-induced obesity in C57BL/6 mice.

OBJECTIVE: High-fat diets cause obesity in male mice; however, the underlying mechanisms remain controversial. Here, three contrasting ideas were assessed: hedonic overdrive, reverse causality, and passive overconsumption models. METHODS: A total of 12 groups of 20 individually housed 12-week-old C57BL/6 male mice were exposed to 12 high-fat diets with varying fat content from 40% to 80% (by calories), protein content from 5% to 30%, and carbohydrate content from 8.4% to 40%. Body weight and food intake were monitored for 30 days after 7 days at baseline on a standard low-fat diet. RESULTS: After exposure to the diets, energy intake increased first, and body weight followed later. Intake then declined. The peak energy intake was dependent on both dietary protein and carbohydrate, but not the dietary fat and energy density, whereas the rate of decrease in intake was only related to dietary protein. On high-fat diets, the weight of food intake declined, but despite this average reduction of 14.4 g in food intake, they consumed, on average, 357 kJ more energy than at baseline. CONCLUSIONS: The hedonic overdrive model fit the data best. The other two models were not supported.

Lipid profile, lipid ratios, apolipoproteins, and risk of cardiometabolic multimorbidity in men: The Kuopio Ischaemic Heart Disease Risk Factor Study.

The blood level of lipids, apolipoproteins, and lipid ratios are important predictors of some chronic diseases. However, their association with cardiometabolic multimorbidity (CMM) is less known. We evaluated a wide range of lipid profiles and lipid ratios, including low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein-cholesterol (VLDL-C), high-density lipoprotein-cholesterol (HDL-C), and apoA1 and B, as well triglyceride and total cholesterol with risk of incident CMM. In 1728 men aged 52.5 ± 5.2 years from the Kuopio Ischaemic Heart Disease were included in this study. We defined CMM as coexisting of two or more of stroke, type 2 diabetes mellitus (T2D), coronary heart disease (CHD). A Cox proportional hazard regression method was applied to evaluate the risk of CMM against the exposures. During the mean follow-up of 22.4 years, 335 men suffered from CMM conditions. Higher serum triglyceride and VLDL concentrations were associated with a higher risk of coexisting T2D-CHD (HRs 1.99 (95% CI, 1.12-3.53) and HRs 1.79 (95% CI, 1.04-3.11), respectively. Whereas higher HDL was associated with lower incident [HRs 0.49 (95% CI, 0.40-1.00)]. The HRs for coexisting T2D-CHD was 2.02 (95% CI, 1.01-3.07) for total cholesterol/HDL-C, 1.85 (95% CI, 1.04-3.29) for triglyceride/HDL-C, 1.69 (95% CI, 1.01-2.31) for Non-HDL-C/HDL-C, and 1.89 (95% CI, 1.03-2.46) for apoB/apoA1. In contrast, serum LDL-C/apoB ratios were inversely associated with the risk of coexisting T2D-CHD [HRs 0.50 (95% CI, 0.28-0.90)]. No associations were observed between our exposures and other CMM conditions. In conclusion, elevated triglyceride, VLDL-C, total cholesterol/HDL-C, TG/HDL-C, apoB/apoA1 as well as lower LDL-C/apoB were independently associated with the higher risk of T2D-CHD coexistence.

The potential role of statins in preeclampsia and dyslipidemia during gestation: a narrative review.

INTRODUCTION: Statins have several pleiotropic effects that have the potential to be beneficial during pregnancy. This study evaluates the available evidence for the teratogenicity of statins, and their utility in treating preeclampsia and dyslipidemia in pregnancy, as good alternatives in these domains are currently lacking. AREAS COVERED: The possible teratogenicity of statins is a primary focus of this paper. We also evaluated for some possible non-teratogenic effects, such as changes in birth weight and rates of spontaneous abortion, among mothers exposed to statins during pregnancy. Regarding potential uses, this study mainly discusses statin utility in preventing and treating preeclampsia and treating dyslipidemia in pregnancy. Within the latter, we explore the relationship between dyslipidemia and preeclampsia, the potential consequences of delaying statin therapy where indicated, and the impact of supra-physiological levels of cholesterol in utero on offspring. The literature search was conducted using Embase, Web of Science, PubMed, and Scopus. EXPERT OPINION: Based on current evidence, statins are likely not teratogenic. Limited, but promising evidence exists for their efficacy in treating and preventing preeclampsia. In utero exposure to high cholesterol may negatively impact offspring, and should be thoroughly investigated.

Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

BACKGROUND: Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. OBJECTIVE: We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. METHODS: The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. RESULTS: Of the 10568 eligible participants, 48.0% (n=5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p<0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (ß-coefficient= -0.012, p=0.056). CONCLUSION: The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

Relationship between long noncoding RNAs and physiological risk factors of cardiovascular disease.

Long noncoding ribonucleic acids (lncRNAs) are an important category of noncoding RNAs that play crucial roles in controlling the expression of genes in health and in a range of illnesses including cardiovascular disease. A large body of genetic, experimental, and epidemiologic evidence suggests roles for an increasing number of lncRNAs in the regulation of metabolism, lipid profile, inflammation, and glucose metabolism in type II diabetes. Importantly, it has been suggested that lncRNAs can regulate chromatin alteration, messenger RNA stability, microRNA action, and can control transcription factors. We aimed to highlight emerging concepts, based on the most current knowledge, regarding the roles of lncRNA in the regulation of cardiovascular risk factors such as lipid profile, glucose homeostasis, and inflammation.