Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis

Hoeke, Geerte; Wang, Yanan; Dam, Anke; Mol, Isabel M.; Gart, Eveline; Klop, Henk G.; Berg, Susan M. van den; Pieterman, Elsbet H.; Princen, H.M.G.; Groen, Albert K.; Rensen, Patrick C.N.; Berbée, Jimmy F.P.; Boon, Mariëtte R.

doi:10.1016/j.atherosclerosis.2017.10.030

Cited by 22 publications

(28 citation statements)

References 34 publications

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“…Angiopoietin-like 4 (ANGPTL4) is down-regulated in BAT during cold exposure in mice, leading to LPL-stimulated TG lipolysis and fatty acid uptake in BAT ( 146 ). Activated BAT in mice stimulates the formation of lipoprotein remnants from more buoyant TRL ( 147 ). Thus, in rodents, metabolically active BAT exerts significant impact on circulating TRL metabolism.…”

Section: Energy Substrates Utilization By Batmentioning

confidence: 99%

Brown Adipose Tissue Energy Metabolism in Humans

et al. 2018

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The demonstration of metabolically active brown adipose tissue (BAT) in humans primarily using positron emission tomography coupled to computed tomography (PET/CT) with the glucose tracer 18-fluorodeoxyglucose (18FDG) has renewed the interest of the scientific and medical community in the possible role of BAT as a target for the prevention and treatment of obesity and type 2 diabetes (T2D). Here, we offer a comprehensive review of BAT energy metabolism in humans. Considerable advances in methods to measure BAT energy metabolism, including nonesterified fatty acids (NEFA), chylomicron-triglycerides (TG), oxygen, Krebs cycle rate, and intracellular TG have led to very good quantification of energy substrate metabolism per volume of active BAT in vivo. These studies have also shown that intracellular TG are likely the primary energy source of BAT upon activation by cold. Current estimates of BAT's contribution to energy expenditure range at the lower end of what would be potentially clinically relevant if chronically sustained. Yet, 18FDG PET/CT remains the gold-standard defining method to quantify total BAT volume of activity, used to calculate BAT's total energy expenditure. Unfortunately, BAT glucose metabolism better reflects BAT's insulin sensitivity and blood flow. It is now clear that most glucose taken up by BAT does not fuel mitochondrial oxidative metabolism and that BAT glucose uptake can therefore be disconnected from thermogenesis. Furthermore, BAT thermogenesis is efficiently recruited upon repeated cold exposure, doubling to tripling its total oxidative capacity, with reciprocal reduction of muscle thermogenesis. Recent data suggest that total BAT volume may be much larger than the typically observed 50–150 ml with 18FDG PET/CT. Therefore, the current estimates of total BAT thermogenesis, largely relying on total BAT volume using 18FDG PET/CT, may underestimate the true contribution of BAT to total energy expenditure. Quantification of the contribution of BAT to energy expenditure begs for the development of more integrated whole body in vivo methods.

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Section: Energy Substrates Utilization By Batmentioning

confidence: 99%

Brown Adipose Tissue Energy Metabolism in Humans

et al. 2018

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“…Rapid thrombus aspiration or PCI is the first choice in patients with acute myocardial infarction, and the routine treatment is anticoagulation and thrombolysis (3,4). However, it has been found in clinic that even if infarction-related blood vessels were opened at first occurence, not all cardiomyocytes could obtain effective blood perfusion (5), which led to poor prognosis. When acute myocardial infarction occurs, how to reduce thrombosis and increase myocardial blood supply is a hot research topic at present (6).…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin combined with routine therapy on HIF-1, VEGF concentration and cardiac function in rats with acute myocardial infarction

Zhang

2020

Exp Ther Med

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Effect of atorvastatin combined with routine therapy on the expression of hypoxia inducible factor (HIF-1) and vascular endothelial growth factor (VEGF) in rats with acute myocardial infarction (AMI) and its therapeutic effect were investigated. The rat models of acute myocardial infarction were established and divided into routine therapy, study, model, single drug and control group according to the treatment plan, with 10 cases in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of HIF-1 and VEGF in serum of rats before treatment (T0), and 3 days (T1), 5 days (T2) and 7 days (T3) after treatment, and the cardiac function was measured at the same time. The concentrations of HIF-1 and VEGF in serum of the study group and the routine therapy group after treatment were significantly higher than those before treatment. The concentrations of HIF-1 and VEGF in serum of model group at T0 were significantly lower than those at T3 (P<0.05). After treatment, the concentrations of HIF-1 and VEGF in serum of the study group were significantly higher than those of the routine therapy, the model and the control group (P<0.05). One week after administration, there were significant differences in the left ventricular function among the five groups (P<0.001). The left ventricular function in the study group was better than that in the routine therapy, model and control group. The levels of HIF-1 and VEGF in the serum of rats with myocardial infarction were negatively correlated with LVIDs and LVIDd, and positively correlated with LVEF% and LVFS%. In conclusion, atorvastatin combined with routine therapy can better reduce serum HIF-1 and VEGF levels and improve the left ventricular function in rats than routine therapy.

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“…It was reported that atorvastatin had an inhibitory effect on adipocyte differentiation which might contribute to pleiotropic actions of statins [25]. Additionally, atorvastatin treatment could accelerate the hepatic uptake of cholesterol-enriched lipoprotein remnants generated by BAT activation, thereby increasing the lipidlowering and anti-atherogenic effect [26]. However, to date there has been little research elucidating whether co-treatment of statins could have lipid-lowering effects though intervening in BAT thermogenesis.…”

Section: Introductionmentioning

confidence: 99%

Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

Liu

Feng

Deng

et al. 2020

BMC Pharmacol Toxicol

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Background: Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated. Methods: To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O + S), or vehicle (control) for 5 weeks. Results: Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O + S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O + S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by cotreatment with O + B. Conclusions: Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.

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Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis

Cited by 22 publications

References 34 publications

Brown Adipose Tissue Energy Metabolism in Humans

Brown Adipose Tissue Energy Metabolism in Humans

Atorvastatin combined with routine therapy on HIF-1, VEGF concentration and cardiac function in rats with acute myocardial infarction

Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

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