Impact of drug distribution into adipose on tissue function: The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib as a test case

AbstractAnacetrapib is an inhibitor of cholesteryl ester transfer protein (CETP) previously under development as a lipid ‐modifying agent that reduces LDL‐cholesterol and increases HDL‐cholesterol in hypercholesterolemic patients. Anacetrapib demonstrates a long terminal half‐life and accumulates in adipose tissue, which contributes to a long residence time of anacetrapib. Given our previous report that anacet rapib distributes into the lipid droplet of adipose tissue, we sought to understand whether anacetrapib affected adipose function, using a diet‐induced obese (DIO) mouse model. Following 20 weeks of treatment with anacetrapib (100 mg/kg/day), levels of the drug increased to approximately 0.6 mm ol/L in white adipose tissue. This level of anacetrapib was not associated with any impairment in adipose functionality as evidenced by a lack of any reduction in biomarkers of adipose functionality (plasma adiponectin, leptin, insulin; adipose adiponectin, leptin mRNA). In DIO wild‐type (WT) mice treated with anacetrapib for 2 weeks and then subjected to 30% food restriction during washout to induce weight loss (18%) and fat mass loss (7%), levels of anacetrapib in adipose and plasma were not different between food restricted and ad lib‐fed mice. These data indicate that despite depositi on and long‐term residence of ~0.6 mmol/L levels of anacetrapib in adipose tissue, adipose tissue function appears to be unaffected in mice. In addition,...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research

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Authors: Mühleck F, Laufs U Abstract Coronary artery disease (CAD) is the most frequent cause of morbidity and mortality worldwide. Lifestyle modifications and drug treatment of cardiovascular risk factors are able to effectively prevent CAD. The basis of prevention is the assessment of the individual cardiovascular risk, e.g. by using a validated risk score. Documented evidence for prevention of CAD is available for the control of hypertension using angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB) and calcium antagonists, for the treatment of hypercholesterolemia using ...
Source: Herz - Category: Cardiology Tags: Herz Source Type: research
The lymphatic system is a parallel circulatory system responsible for moving fluid, immune cells, and a range of vital molecules around the body. It is of particular importance to immune function, allowing components of the immune system to carry messages from place to place in the body, and communicate and coordinate the immune response at the hubs known as lymph nodes. Like all tissues in the body, the lymphatic system is negatively impacted by aging, and this has widespread detrimental effects throughout the body and brain. For example, lymph nodes become disrupted in structure and function by the presence of sen...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
ConclusionsSeveral risk factors may play a role in evolution of MS. Our results show that smoking status, probably due to chronic vascular and neurotoxic effects of the cigarette components, can affect the brain damage from the early stages of MS. No association was observed with the other explored modifiable risk factors, although an effect due to the small sample size cannot be excluded.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
CONCLUSIONS: This novel research shows that MHO children have greater aBMD than their MUO peers. Furthermore, both MVPA and more importantly CRF seem to partially explain these findings. PMID: 31822016 [PubMed - as supplied by publisher]
Source: Pediatric Research - Category: Pediatrics Authors: Tags: Pediatr Res Source Type: research
(Medical College of Georgia at Augusta University) Eight months of daily, afterschool physical activity in previously inactive 8- to 11-year-olds with obesity and overweight improved key measures of their cardiovascular health like good cholesterol levels, aerobic fitness and percent body fat, but didn't improve others like arterial stiffness, an early indicator of cardiovascular risk, Medical College of Georgia investigators report.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ska M Abstract In the study, 305 patients of both genders were enrolled and divided into three groups: obese (BMI> 30 kg/m2), patients who were diagnosed type 2 diabetes mellitus (T2DM), and control, normal weight healthy volunteers. At least one of ten different phthalate metabolites was determined in the urine samples of 49.84% all enrolled participants. In the obese subgroup, the sum of all urinary phthalate metabolites was positively associated with TG levels (p = 0.031) together with derived TC/HDL and TG/HDL ratios (p = 0.023 and 0.015), respectively. Urinary MEP concentration was positively correlated wi...
Source: Environmental Science and Pollution Research International - Category: Environmental Health Authors: Tags: Environ Sci Pollut Res Int Source Type: research
Abstract The purpose of this study is to determine whether or not trehangelin A (THG-A) is effective in treating the metabolic clinical condition caused by a high-fat diet. The body weight, epididymal adipose volume, alanine transaminase (ALT), total-cholesterol (T-CHO), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and glucose concentrations in serum increased in mice fed a high-fat diet compared to mice fed a control diet. On the other hand, adiponectin level in serum of mice fed a high-fat diet decreased compared to that of control mice. When mice fed a high-fat diet were intraperitoneally adm...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
euwenhuijsen Manuel Franco The aim of this study is to evaluate the relationship between the density of green spaces at different buffer sizes (300, 500, 1000 and 1500 m) and cardiovascular risk factors (obesity, hypertension, high cholesterol, and diabetes) as well as to study if the relationship is different for males and females. We conducted cross-sectional analyses using the baseline measures of the Heart Healthy Hoods study (N = 1625). We obtained data on the outcomes from clinical diagnoses, as well as anthropometric and blood sample measures. Exposure data on green spaces density at different buffer sizes wer...
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
Discussion and conclusion: MDE possesses substantial antidiabetic activity, especially in lipid disorder regulation. This suggests that the use of MDE can be generalized to broader pharmacological studies, such as obesity and hyperlipidaemia. PMID: 31794270 [PubMed - in process]
Source: Pharmaceutical Biology - Category: Drugs & Pharmacology Tags: Pharm Biol Source Type: research
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