Adipocyte Differentiation-Related Protein and OXPAT in Rat and Human Skeletal Muscle: Involvement in Lipid Accumulation and Type 2 Diabetes Mellitus
Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism...
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| Published in | The journal of clinical endocrinology and metabolism Vol. 94; no. 10; pp. 4077 - 4085 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Bethesda, MD
Oxford University Press
01.10.2009
Endocrine Society |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-972X 1945-7197 1945-7197 |
| DOI | 10.1210/jc.2009-0352 |
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| Abstract | Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues.
Objective: This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity.
Design: Muscle OXPAT and ADRP protein content was examined during the development of insulin resistance in Zucker diabetic fatty (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects. Furthermore, we examined the effect of 8 wk of insulin sensitizing by rosiglitazone on muscle OXPAT and ADRP content.
Results: OXPAT and ADRP protein expression is muscle fiber type specific in humans and rats, with highest protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein content was 2- to 3-fold higher in ZDF rats during the progression of type 2 diabetes than in lean normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL level, was not different between type 2 diabetes patients and control subjects. ADRP content was negatively associated with insulin-stimulated glucose uptake (r = −0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle OXPAT (−29%) and ADRP (−28%) content in diabetes patients, without affecting IMCL.
Conclusions: These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes.ADRP and OXPAT proteins show fiber type-specific distribution in rat and human skeletal muscle, and are involved in lipid accumulation and type 2 diabetes mellitus. |
|---|---|
| AbstractList | Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues. Objective: This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity. Design: Muscle OXPAT and ADRP protein content was examined during the development of insulin resistance in Zucker diabetic fatty (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects. Furthermore, we examined the effect of 8 wk of insulin sensitizing by rosiglitazone on muscle OXPAT and ADRP content. Results: OXPAT and ADRP protein expression is muscle fiber type specific in humans and rats, with highest protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein content was 2- to 3-fold higher in ZDF rats during the progression of type 2 diabetes than in lean normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL level, was not different between type 2 diabetes patients and control subjects. ADRP content was negatively associated with insulin-stimulated glucose uptake (r = −0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle OXPAT (−29%) and ADRP (−28%) content in diabetes patients, without affecting IMCL. Conclusions: These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes.ADRP and OXPAT proteins show fiber type-specific distribution in rat and human skeletal muscle, and are involved in lipid accumulation and type 2 diabetes mellitus. A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues. This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity. Muscle OXPAT and ADRP protein content was examined during the development of insulin resistance in Zucker diabetic fatty (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects. Furthermore, we examined the effect of 8 wk of insulin sensitizing by rosiglitazone on muscle OXPAT and ADRP content. OXPAT and ADRP protein expression is muscle fiber type specific in humans and rats, with highest protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein content was 2- to 3-fold higher in ZDF rats during the progression of type 2 diabetes than in lean normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL level, was not different between type 2 diabetes patients and control subjects. ADRP content was negatively associated with insulin-stimulated glucose uptake (r = -0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle OXPAT (-29%) and ADRP (-28%) content in diabetes patients, without affecting IMCL. These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes. Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues. Objective: This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity. Design: Muscle OXPAT and ADRP protein content was examined during the development of insulin resistance in Zucker diabetic fatty (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects. Furthermore, we examined the effect of 8 wk of insulin sensitizing by rosiglitazone on muscle OXPAT and ADRP content. Results: OXPAT and ADRP protein expression is muscle fiber type specific in humans and rats, with highest protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein content was 2- to 3-fold higher in ZDF rats during the progression of type 2 diabetes than in lean normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL level, was not different between type 2 diabetes patients and control subjects. ADRP content was negatively associated with insulin-stimulated glucose uptake (r = −0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle OXPAT (−29%) and ADRP (−28%) content in diabetes patients, without affecting IMCL. Conclusions: These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes.ADRP and OXPAT proteins show fiber type-specific distribution in rat and human skeletal muscle, and are involved in lipid accumulation and type 2 diabetes mellitus. A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues.SETTINGA disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues.This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity.OBJECTIVEThis study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity.Muscle OXPAT and ADRP protein content was examined during the development of insulin resistance in Zucker diabetic fatty (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects. Furthermore, we examined the effect of 8 wk of insulin sensitizing by rosiglitazone on muscle OXPAT and ADRP content.DESIGNMuscle OXPAT and ADRP protein content was examined during the development of insulin resistance in Zucker diabetic fatty (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects. Furthermore, we examined the effect of 8 wk of insulin sensitizing by rosiglitazone on muscle OXPAT and ADRP content.OXPAT and ADRP protein expression is muscle fiber type specific in humans and rats, with highest protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein content was 2- to 3-fold higher in ZDF rats during the progression of type 2 diabetes than in lean normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL level, was not different between type 2 diabetes patients and control subjects. ADRP content was negatively associated with insulin-stimulated glucose uptake (r = -0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle OXPAT (-29%) and ADRP (-28%) content in diabetes patients, without affecting IMCL.RESULTSOXPAT and ADRP protein expression is muscle fiber type specific in humans and rats, with highest protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein content was 2- to 3-fold higher in ZDF rats during the progression of type 2 diabetes than in lean normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL level, was not different between type 2 diabetes patients and control subjects. ADRP content was negatively associated with insulin-stimulated glucose uptake (r = -0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle OXPAT (-29%) and ADRP (-28%) content in diabetes patients, without affecting IMCL.These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes.CONCLUSIONSThese results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes. Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues. Objective: This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity. Design: Muscle OXPAT and ADRP protein content was examined during the development of insulin resistance in Zucker diabetic fatty (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects. Furthermore, we examined the effect of 8 wk of insulin sensitizing by rosiglitazone on muscle OXPAT and ADRP content. Results: OXPAT and ADRP protein expression is muscle fiber type specific in humans and rats, with highest protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein content was 2- to 3-fold higher in ZDF rats during the progression of type 2 diabetes than in lean normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL level, was not different between type 2 diabetes patients and control subjects. ADRP content was negatively associated with insulin-stimulated glucose uptake (r = -0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle OXPAT (-29%) and ADRP (-28%) content in diabetes patients, without affecting IMCL. Conclusions: These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes |
| Author | Schaart, Gert Jorgensen, Johanna A. Mensink, Marco Schrauwen, Patrick Hesselink, Matthijs K.C. Minnaard, Ronnie Lenaers, Ellen |
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| Keywords | Endocrinopathy Type 2 diabetes Human Adipocyte Obesity Nutrition Rat Rodentia Nutrition disorder Lipids Metabolic diseases Cell differentiation Striated muscle Accumulation Protein Vertebrata Mammalia Animal Differentiation Endocrinology Nutritional status |
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| PublicationDecade | 2000 |
| PublicationPlace | Bethesda, MD |
| PublicationPlace_xml | – name: Bethesda, MD – name: United States – name: Washington |
| PublicationTitle | The journal of clinical endocrinology and metabolism |
| PublicationTitleAlternate | J Clin Endocrinol Metab |
| PublicationYear | 2009 |
| Publisher | Oxford University Press Endocrine Society |
| Publisher_xml | – name: Oxford University Press – name: Endocrine Society |
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| Snippet | Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin,... A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte... |
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| SubjectTerms | Adipocytes Animals Biological and medical sciences Biomarkers - metabolism Carrier Proteins Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - metabolism Diabetes. Impaired glucose tolerance DNA-Binding Proteins - metabolism droplets Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance fatty rats Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Humans Hypoglycemic Agents - pharmacology inhibition Insulin resistance Intracellular Signaling Peptides and Proteins - metabolism Intracellular Signaling Peptides and Proteins - physiology Lipid Metabolism Lipids magnetic-resonance-spectroscopy Medical sciences Membrane Proteins - chemical synthesis Membrane Proteins - metabolism Metabolism Muscle Proteins - metabolism Muscle, Skeletal - metabolism Musculoskeletal system pathogenesis Perilipin-1 Perilipin-2 Perilipin-3 Perilipin-5 Phosphoproteins - metabolism Pregnancy Proteins - metabolism progression Protein folding Protein turnover Proteins Rats Rosiglitazone sensitivity Skeletal muscle Thiazolidinediones - pharmacology triglyceride content Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: endocrinology Vesicular Transport Proteins |
| Title | Adipocyte Differentiation-Related Protein and OXPAT in Rat and Human Skeletal Muscle: Involvement in Lipid Accumulation and Type 2 Diabetes Mellitus |
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