Impact of simvastatin on adipose tissue: Pleiotropic effects in vivo

Tayeba Khan, Mark P. Hamilton, Dorothy I. Mundy, Streamson C. Chua, Jr., Philipp E. Scherer

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 livermaybetargeted 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.

Original languageEnglish (US)
Pages (from-to)5262-5272
Number of pages11
JournalEndocrinology
Volume150
Issue number12
DOIs
StatePublished - Dec 2009

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Adipose Tissue
Adiponectin
Adipocytes
Insulin Resistance
Anti-Inflammatory Agents
Cholesterol
Adipokines
Secretory Pathway
Adiposity
Pharmaceutical Preparations
LDL Cholesterol
Histology
Antioxidants
Molecular Weight
Cell Membrane
Insulin
Inflammation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Khan, T., Hamilton, M. P., Mundy, D. I., Chua, Jr., S. C., & Scherer, P. E. (2009). Impact of simvastatin on adipose tissue: Pleiotropic effects in vivo. Endocrinology, 150(12), 5262-5272. https://doi.org/10.1210/en.2009-0603

Impact of simvastatin on adipose tissue : Pleiotropic effects in vivo. / Khan, Tayeba; Hamilton, Mark P.; Mundy, Dorothy I.; Chua, Jr., Streamson C.; Scherer, Philipp E.

In: Endocrinology, Vol. 150, No. 12, 12.2009, p. 5262-5272.

Research output: Contribution to journalArticle

Khan, T, Hamilton, MP, Mundy, DI, Chua, Jr., SC & Scherer, PE 2009, 'Impact of simvastatin on adipose tissue: Pleiotropic effects in vivo', Endocrinology, vol. 150, no. 12, pp. 5262-5272. https://doi.org/10.1210/en.2009-0603
Khan, Tayeba ; Hamilton, Mark P. ; Mundy, Dorothy I. ; Chua, Jr., Streamson C. ; Scherer, Philipp E. / Impact of simvastatin on adipose tissue : Pleiotropic effects in vivo. In: Endocrinology. 2009 ; Vol. 150, No. 12. pp. 5262-5272.
@article{c730e1a307d2425b996eceea10bd3c97,
title = "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 livermaybetargeted 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.",
author = "Tayeba Khan and Hamilton, {Mark P.} and Mundy, {Dorothy I.} and {Chua, Jr.}, {Streamson C.} and Scherer, {Philipp E.}",
year = "2009",
month = "12",
doi = "10.1210/en.2009-0603",
language = "English (US)",
volume = "150",
pages = "5262--5272",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "12",

}

TY - JOUR

T1 - Impact of simvastatin on adipose tissue

T2 - Pleiotropic effects in vivo

AU - Khan, Tayeba

AU - Hamilton, Mark P.

AU - Mundy, Dorothy I.

AU - Chua, Jr., Streamson C.

AU - Scherer, Philipp E.

PY - 2009/12

Y1 - 2009/12

N2 - 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 livermaybetargeted 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.

AB - 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 livermaybetargeted 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.

UR - http://www.scopus.com/inward/record.url?scp=71949103387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=71949103387&partnerID=8YFLogxK

U2 - 10.1210/en.2009-0603

DO - 10.1210/en.2009-0603

M3 - Article

C2 - 19819942

AN - SCOPUS:71949103387

VL - 150

SP - 5262

EP - 5272

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 12

ER -