Impact of Simvastatin on Adipose Tissue: Pleiotropic Effects in Vivo

Abstract Statins belong to a class of drugs well known for their ability to reduce circulating low-density lipoprotein cholesterol. In addition to cholesterol lowering, they also exhibit potential antiinflammatory and antioxidant properties, suggesting that tissues other than liver may be targeted by statins to exert their beneficial metabolic effects. Adipocytes have received very little attention as a potential target of these drugs, possibly because adipocytes are not a major source of biosynthetic cholesterol. Here, we examine the effects of simvastatin on the secretory pathway, inflammation, and cellular metabolism of adipocytes as well as on whole-body insulin sensitivity. We find that statins have a selective effect on the secretion of the insulin-sensitizing adipokine adiponectin by reducing circulating levels of the high-molecular-weight form of adiponectin specifically with a concomitant increase in intracellular adiponectin levels. However, these effects on adiponectin do not translate into changes in metabolism or whole-body insulin sensitivity, potentially due to additional antiinflammatory properties of statins. In addition, ob/ob mice treated with statins have reduced adiposity and an altered ultrastructure of the plasma membrane with respect to caveolar histology. Our data demonstrate that statins have major effects on the cellular physiology of the adipocyte on multiple levels.

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Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy

Acta Endocrinologica ◽

10.1530/eje-10-0317 ◽

2010 ◽

Vol 163 (3) ◽

pp. 361-368 ◽

Cited By ~ 19

Author(s):

Claudia Giavoli ◽

Emanuele Ferrante ◽

Eriselda Profka ◽

Luca Olgiati ◽

Silvia Bergamaschi ◽

...

Keyword(s):

Insulin Sensitivity ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Metabolic Effects ◽

Functional Difference ◽

Fat Percentage ◽

Rhgh Therapy ◽

The Impact

ObjectiveA common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy.DesignProspective study of GHD patients evaluated before and during short- (1 year,n=100) and long-term (5 years,n=50) rhGH therapy.MethodsEffects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant.ResultsThe different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low-density lipoprotein cholesterol was also observed.ConclusionThe functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults.

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Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases

Cells ◽

10.3390/cells9091932 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1932

Author(s):

Chiara D’Angelo ◽

Sara Franceschelli ◽

José Luis Quiles ◽

Lorenza Speranza

Keyword(s):

Cardiovascular Health ◽

Biological Effects ◽

Low Density Lipoprotein ◽

Antioxidant Properties ◽

Density Lipoprotein ◽

In Vivo Models ◽

And Oxidative Stress

The growing incidence of cardiovascular disease (CVD) has promoted investigations of natural molecules that could prevent and treat CVD. Among these, hydroxytyrosol, a polyphenolic compound of olive oil, is well known for its antioxidant, anti-inflammatory, and anti-atherogenic effects. Its strong antioxidant properties are due to the scavenging of radicals and the stimulation of synthesis and activity of antioxidant enzymes (SOD, CAT, HO-1, NOS, COX-2, GSH), which also limit the lipid peroxidation of low-density lipoprotein (LDL) cholesterol, a hallmark of atherosclerosis. Lowered inflammation and oxidative stress and an improved lipid profile were also demonstrated in healthy subjects as well as in metabolic syndrome patients after hydroxytyrosol (HT) supplementation. These results might open a new therapeutic scenario through personalized supplementation of HT in CVDs. This review is the first attempt to collect together scientific literature on HT in both in vitro and in vivo models, as well as in human clinical studies, describing its potential biological effects for cardiovascular health.

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Whole-body insulin sensitivity, low-density lipoprotein (LDL) particle size, and oxidized LDL in overweight, nondiabetic men

Metabolism ◽

10.1053/meta.2002.35577 ◽

2002 ◽

Vol 51 (11) ◽

pp. 1478-1483 ◽

Cited By ~ 21

Author(s):

Richard C. Ho ◽

Kevin Davy ◽

Brenda Davy ◽

Christopher L. Melby

Keyword(s):

Particle Size ◽

Insulin Sensitivity ◽

Oxidized Ldl ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Whole Body ◽

Low Density ◽

Ldl Particle Size

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Comparative studies on the hypoglycemic and antioxidant activities of Vernonia amygdalina delile and Baccharoides tenoreana olive in alloxan-induced hyperglycemic rats

Clinical Phytoscience ◽

10.1186/s40816-021-00330-z ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Samuel Chijioke Attama ◽

Patrick Emeka Aba ◽

Chinwe Uchechukwu Asuzu ◽

Isaac Uzoma Asuzu

Keyword(s):

Antioxidant Activities ◽

Islet Cells ◽

Low Density Lipoprotein ◽

Fasting Blood Glucose ◽

Antioxidant Properties ◽

Density Lipoprotein ◽

Vernonia Amygdalina ◽

Once Daily ◽

Alloxan Monohydrate

Abstract Background Vernonia amygdalina is a bitter culinary vegetable known to possess anti-diabetic principle. Baccharoides tenoreana belonging to the same species as V. amygdalina, is also used in cooking soup and it is comparatively non-bitter. However, its glycemic properties have not been studied. This study becomes imperative to find out if B. tenoreana possesses hypoglycemic and antioxidant properties and how it compares with V. amygdalina. Should B. tenoreana be better than V. amygdalina, it should be preferable since it is non-bitter and can comfortably be taken compared to V. amygdalina. This study investigated the comparative hypoglycemic and antioxidant potentials of V. amygdalina (VA) and B. tenoreana (BT). Methods Thirty male Albino wistar rats assigned into six groups of five rats per group were used for the study. Diabetes was induced in groups B-F rats by a single intraperitoneal injection of alloxan monohydrate at 160 mg/kg. Groups C-E rats were treated with VA (200 mg/kg), BT (200 mg/kg) and combination of VA & BT (100 mg/kg each) respectively. Group F rats were administered glibenclamide (2 mg/kg) whereas groups A and B rats were given distilled water. All treatments were through the oral administration, once daily for 21 consecutive days. Fasting blood glucose (FBG) levels were determined after 1 h, 3 h, 6 h, 24 h, 7 days, 14 days and 21 days while lipid profile, in vivo antioxidant and pancreatic histomorphology were assessed on day 21 post-treatment. Results The VA-treated rats recorded marginally reduced FBG, malondialdehyde and low-density lipoprotein levels when compared to the counterpart treated with BT. The high-density lipoprotein values were significantly higher in VA-treated rats than in BT-treated rats. The histomorphology of the pancreas of VA-treated rats expressed more islet cells compared to the counterpart treated with VT. Conclusion Both VA and BT exhibited hypoglycemic and antioxidant activities with varying potencies.

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Oxidation of Plasma Low-Density Lipoprotein Accelerates Its Accumulation and Degradation in the Arterial Wall In Vivo

Circulation ◽

10.1161/01.cir.94.7.1698 ◽

1996 ◽

Vol 94 (7) ◽

pp. 1698-1704 ◽

Cited By ~ 46

Author(s):

Klaus Juul ◽

Lars B. Nielsen ◽

Klaus Munkholm ◽

Steen Stender ◽

Børge G. Nordestgaard

Keyword(s):

Arterial Wall ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density

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Interaction of 4-hydroxynonenal-modified low-density lipoproteins with the fibroblast apolipoprotein B/E receptor

Biochemical Journal ◽

10.1042/bj2340245 ◽

1986 ◽

Vol 234 (1) ◽

pp. 245-248 ◽

Cited By ~ 31

Author(s):

W Jessup ◽

G Jurgens ◽

J Lang ◽

H Esterbauer ◽

R T Dean

Keyword(s):

Apolipoprotein B ◽

Negative Charge ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Low Density ◽

Lipid Peroxidation Product ◽

Modified Low Density Lipoproteins ◽

Peroxidation Product

The incorporation of the lipid peroxidation product 4-hydroxynonenal into low-density lipoprotein (LDL) increases the negative charge of the particle, and decreases its affinity for the fibroblast LDL receptor. It is suggested that this modification may occur in vivo, and might promote atherogenesis.

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