Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity

Mitchell Sitnick, Mahesh K. Basantani, Lingzhi Cai, Gabriele Schoiswohl, Cynthia F. Yazbeck, Giovanna Distefano, Vladimir Ritov, James P. DeLany, Renate Schreiber, Donna B. Stolz, Noah P. Gardner, Petra C. Kienesberger, Thomas Pulinilkunnil, Rudolf Zechner, Bret H. Goodpaster, Paul Coen, Erin E. Kershaw

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete's paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.

Original languageEnglish
Pages (from-to)3350-3361
Number of pages12
JournalDiabetes
Volume62
Issue number10
DOIs
StatePublished - 1 Oct 2013

Fingerprint

Skeletal Muscle
Triglycerides
Hydrolysis
Obesity
Lipase
Insulin Resistance
Athletes
Homeostasis
Insulin
Lipids
Muscles
Lipolysis
High Fat Diet
Phenotype
Glucose

Cite this

Sitnick, M., Basantani, M. K., Cai, L., Schoiswohl, G., Yazbeck, C. F., Distefano, G., ... Kershaw, E. E. (2013). Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. Diabetes, 62(10), 3350-3361. https://doi.org/10.2337/db13-0500
Sitnick, Mitchell ; Basantani, Mahesh K. ; Cai, Lingzhi ; Schoiswohl, Gabriele ; Yazbeck, Cynthia F. ; Distefano, Giovanna ; Ritov, Vladimir ; DeLany, James P. ; Schreiber, Renate ; Stolz, Donna B. ; Gardner, Noah P. ; Kienesberger, Petra C. ; Pulinilkunnil, Thomas ; Zechner, Rudolf ; Goodpaster, Bret H. ; Coen, Paul ; Kershaw, Erin E. / Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. In: Diabetes. 2013 ; Vol. 62, No. 10. pp. 3350-3361.
@article{f2178bc44d1442608078e33534d9d337,
title = "Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity",
abstract = "Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete's paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.",
author = "Mitchell Sitnick and Basantani, {Mahesh K.} and Lingzhi Cai and Gabriele Schoiswohl and Yazbeck, {Cynthia F.} and Giovanna Distefano and Vladimir Ritov and DeLany, {James P.} and Renate Schreiber and Stolz, {Donna B.} and Gardner, {Noah P.} and Kienesberger, {Petra C.} and Thomas Pulinilkunnil and Rudolf Zechner and Goodpaster, {Bret H.} and Paul Coen and Kershaw, {Erin E.}",
year = "2013",
month = "10",
day = "1",
doi = "10.2337/db13-0500",
language = "English",
volume = "62",
pages = "3350--3361",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "10",

}

Sitnick, M, Basantani, MK, Cai, L, Schoiswohl, G, Yazbeck, CF, Distefano, G, Ritov, V, DeLany, JP, Schreiber, R, Stolz, DB, Gardner, NP, Kienesberger, PC, Pulinilkunnil, T, Zechner, R, Goodpaster, BH, Coen, P & Kershaw, EE 2013, 'Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity', Diabetes, vol. 62, no. 10, pp. 3350-3361. https://doi.org/10.2337/db13-0500

Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. / Sitnick, Mitchell; Basantani, Mahesh K.; Cai, Lingzhi; Schoiswohl, Gabriele; Yazbeck, Cynthia F.; Distefano, Giovanna; Ritov, Vladimir; DeLany, James P.; Schreiber, Renate; Stolz, Donna B.; Gardner, Noah P.; Kienesberger, Petra C.; Pulinilkunnil, Thomas; Zechner, Rudolf; Goodpaster, Bret H.; Coen, Paul; Kershaw, Erin E.

In: Diabetes, Vol. 62, No. 10, 01.10.2013, p. 3350-3361.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity

AU - Sitnick, Mitchell

AU - Basantani, Mahesh K.

AU - Cai, Lingzhi

AU - Schoiswohl, Gabriele

AU - Yazbeck, Cynthia F.

AU - Distefano, Giovanna

AU - Ritov, Vladimir

AU - DeLany, James P.

AU - Schreiber, Renate

AU - Stolz, Donna B.

AU - Gardner, Noah P.

AU - Kienesberger, Petra C.

AU - Pulinilkunnil, Thomas

AU - Zechner, Rudolf

AU - Goodpaster, Bret H.

AU - Coen, Paul

AU - Kershaw, Erin E.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete's paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.

AB - Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete's paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.

UR - http://www.scopus.com/inward/record.url?scp=84888130465&partnerID=8YFLogxK

U2 - 10.2337/db13-0500

DO - 10.2337/db13-0500

M3 - Article

VL - 62

SP - 3350

EP - 3361

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

ER -

Sitnick M, Basantani MK, Cai L, Schoiswohl G, Yazbeck CF, Distefano G et al. Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. Diabetes. 2013 Oct 1;62(10):3350-3361. https://doi.org/10.2337/db13-0500