Atorvastatin and rosuvastatin improve physiological parameters and alleviate immune dysfunction in metabolic disorders

Lee, Sung-Won; Lee, Young‐Joo; Kim, Jiyeon; An, Jinho; Kim, Kwanghee; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Kim, Kyungjae

doi:10.1016/j.bbrc.2016.08.101

Cited by 17 publications

(17 citation statements)

References 31 publications

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“…The CAF-diet is a robust experimental model of metabolic syndrome that is capable of inducing obesity, glucose intolerance, and inflammation in rats (7,9), and is consistent with the results of our experiments, which showed that the 16-week CAFdiet significantly increased (Po0.05) body weight, serum insulin, glucose, total cholesterol, and triglycerides in Wistar rats (Table 1). These findings reinforced previous studies in which an 8-week CAF-diet increased the same metabolic parameters in Wistar rats (4) and are in line with previous reports linking a high-fat diet to increases in levels of glucose, cholesterol, triglycerides, and insulin (10,11).…”

Section: Discussionsupporting

confidence: 92%

“…The body weight-lowering effect produced by rosuvastatin in rats fed the CAF-diet compared to rats that were only fed the CAFdiet reinforced recent studies that suggested that treatment with rosuvastatin for 6 weeks produces a decreasing tendency in mean body weight of mice fed a high-fat diet. In these studies, the treatment with rosuvastatin decreased the weight of fatty tissue samples and significantly decreased the fat storage in adipose tissue samples (10). The body weight-lowering effect produced by rosuvastatin could be involved with a decrease in plasma levels of leptin, as previously report for pravastatin (12).…”

Section: Discussionsupporting

confidence: 66%

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Possible mechanisms involved in the effect of the subchronic administration of rosuvastatin on endothelial function in rats with metabolic syndrome

Lozano-Cuenca

Valencia-Hernández

López-Canales

et al. 2020

Braz J Med Biol Res

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Metabolic syndrome is a multifaceted condition associated with a greater risk of various disorders (e.g., diabetes and heart disease). In a rat model of metabolic syndrome, an acute in vitro application of rosuvastatin causes relaxation of aortic rings. Since the outcome of a subchronic rosuvastatin treatment is unknown, the present study explored its effect on acetylcholineinduced vasorelaxation of aortic rings from rats with metabolic syndrome. Animals were submitted to a 16-week treatment, including a standard diet, a cafeteria-style diet (CAF-diet), or a CAF-diet with daily rosuvastatin treatment (10 mg/kg). After confirming the development of metabolic syndrome in rats, aortic segments were extracted from these animals (those treated with rosuvastatin and untreated) and the acetylcholine-induced relaxant effect on the corresponding rings was evaluated. Concentration-response curves were constructed for this effect in the presence/absence of L-NAME, ODQ, KT 5823, 4-aminopyridine (4-AP), tetraethylammonium (TEA), apamin plus charybdotoxin, glibenclamide, indomethacin, clotrimazole, and cycloheximide pretreatment. Compared to rings from control rats, acetylcholine-induced vasorelaxation decreased in rings from animals with metabolic syndrome, and was maintained at a normal level in animals with metabolic syndrome plus rosuvastatin treatment. The effect of rosuvastatin was inhibited by L-NAME, ODQ, KT 5823, TEA, apamin plus charybdotoxin, but unaffected by 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. In conclusion, the subchronic administration of rosuvastatin to rats with metabolic syndrome improved the acetylcholine-induced relaxant response, involving stimulation of the NO/cGMP/PKG/Ca 2+-activated K + channel pathway.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 66%

Possible mechanisms involved in the effect of the subchronic administration of rosuvastatin on endothelial function in rats with metabolic syndrome

Lozano-Cuenca

Valencia-Hernández

López-Canales

et al. 2020

Braz J Med Biol Res

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“…Regulation of IL-1β and TGFβ expression may play a key role in the metabolic improvements associated with statin therapy, due to changes in gut microbiota. A previous study reported that statin therapy regulates inflammatory cytokines such as IL-1β, IL-6, and TNF-α (Lee et al, 2016). In the present study, IL-1β and TGFβ expression increased in the ileum, indicating that the regulation of IL-1β and TGFβ is associated with the effect of statins on the alleviation of hyperglycemia, hyperlipidemia, and inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, statins induce the expression of low-density lipoprotein (LDL) receptors and promote the removal of LDL cholesterol from the blood (Young and Fong, 2012). Furthermore, statins have been reported to have anti-inflammatory and immunomodulatory effects (Lee et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Alterations in Gut Microbiota by Statin Therapy and Possible Intermediate Effects on Hyperglycemia and Hyperlipidemia

et al. 2019

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Dysbiosis of the gut microbiota is a contributing factor for obesity-related metabolic diseases such as hyperglycemia and hyperlipidemia. Pharmacotherapy for metabolic diseases involves the modulation of gut microbiota, which is suggested to be a potential therapeutic target. In this study, the modulation of gut microbiota by statins (cholesterol-lowering drugs: atorvastatin and rosuvastatin) was investigated in an aged mouse model of high-fat diet-induced obesity, and the association between gut microbiota and immune responses was described. Atorvastatin and rosuvastatin significantly increased the abundance of the genera Bacteroides, Butyricimonas, and Mucispirillum. Moreover, the abundance of these genera was correlated with the inflammatory response, including levels of IL-1β and TGFβ1 in the ileum. In addition, oral fecal microbiota transplantation with fecal material collected from rosuvastatin-treated mouse groups improved hyperglycemia. From these results, the effect of statins on metabolic improvements could be explained by altered gut microbiota. Our findings suggest that the modulation of gut microbiota by statins has an important role in the therapeutic actions of these drugs.

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“…Cholesterol-manipulation may modulate T cell immunity, which is largely responsible for immune-mediated cancer control. 9, 10, 11 However, previous reports that examined the immune effects of CL at the subcellular level have reached conflicting conclusions. Some reports suggest that membrane cholesterol promotes T cell function.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol-lowering Decreased mTOR Complex 2 Signaling and Enhanced Antitumor Immunity

Wang

You

et al. 2021

Preprint

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SummaryCholesterol-lowering interventions are employed widely and safely to reduce risk of cardiovascular disease. Cholesterol may have complex and opposing effects on immunity. We lowered serum cholesterol to clinically relevant levels in mice and evaluated the final adaptive immune response. Mice treated with oral ezetimibe exhibited enhanced antitumor immunity against syngeneic cancers in a CD8+ lymphocyte-dependent manner, produced immunity that was transferrable through lymphocytes, and enhanced central CD8+ T cell memory. In both mice and patients undergoing prostatectomy, lowering serum cholesterol inhibited mTORC2 signaling in lymphocytes and increased infiltration of CD8+ lymphocytes into prostate tumors. Lymphocyte-specific mTORC2 knockout mice demonstrated enhanced CD8+ lymphocyte function and antitumor capacity. In a prospective clinical trial, cholesterol-lowering intervention prior to prostatectomy decreased the proliferation of normal prostate and low-grade adenocarcinomas. Here, we show that lowering serum cholesterol may be an effective strategy to decrease signaling through mTORC2 and enhance antitumor CD8+ T cell memory.

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Atorvastatin and rosuvastatin improve physiological parameters and alleviate immune dysfunction in metabolic disorders

Cited by 17 publications

References 31 publications

Possible mechanisms involved in the effect of the subchronic administration of rosuvastatin on endothelial function in rats with metabolic syndrome

Possible mechanisms involved in the effect of the subchronic administration of rosuvastatin on endothelial function in rats with metabolic syndrome

Alterations in Gut Microbiota by Statin Therapy and Possible Intermediate Effects on Hyperglycemia and Hyperlipidemia

Cholesterol-lowering Decreased mTOR Complex 2 Signaling and Enhanced Antitumor Immunity

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