Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals

Hongyi Zhou, Xinnuo Lei, Tyler Benson, James Mintz, Xiaojing Xu, Ruth Babette Harris, Neal Lee Weintraub, Xiaoling Wang, Weiqin Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat dietinduced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose β3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning-induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counterregulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in AdmKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and β-adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance.

Original languageEnglish (US)
Pages (from-to)1912-1925
Number of pages14
JournalJournal of Lipid Research
Volume56
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

Congenital Generalized Lipodystrophy
Lipolysis
Energy balance
Adipocytes
Adipose Tissue
Animals
Tissue
White Adipose Tissue
Brown Adipose Tissue
Thermogenesis
Adiposity
Gene Expression Profiling
Cyclic AMP-Dependent Protein Kinases
Adrenergic Agents
Adrenergic Receptors
Energy Metabolism
Insulin Resistance
Fatty Acids
Down-Regulation
Obesity

Keywords

  • Adipose tissue
  • Beta-oxidation
  • Lipolysis and fatty acid metabolism
  • Obesity
  • Triglycerides

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals. / Zhou, Hongyi; Lei, Xinnuo; Benson, Tyler; Mintz, James; Xu, Xiaojing; Harris, Ruth Babette; Weintraub, Neal Lee; Wang, Xiaoling; Chen, Weiqin.

In: Journal of Lipid Research, Vol. 56, No. 10, 01.10.2015, p. 1912-1925.

Research output: Contribution to journalArticle

@article{e33a5a74805b4267b004538bfa5164e9,
title = "Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals",
abstract = "Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat dietinduced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose β3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning-induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counterregulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in AdmKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and β-adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance.",
keywords = "Adipose tissue, Beta-oxidation, Lipolysis and fatty acid metabolism, Obesity, Triglycerides",
author = "Hongyi Zhou and Xinnuo Lei and Tyler Benson and James Mintz and Xiaojing Xu and Harris, {Ruth Babette} and Weintraub, {Neal Lee} and Xiaoling Wang and Weiqin Chen",
year = "2015",
month = "10",
day = "1",
doi = "10.1194/jlr.M060244",
language = "English (US)",
volume = "56",
pages = "1912--1925",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "10",

}

TY - JOUR

T1 - Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals

AU - Zhou, Hongyi

AU - Lei, Xinnuo

AU - Benson, Tyler

AU - Mintz, James

AU - Xu, Xiaojing

AU - Harris, Ruth Babette

AU - Weintraub, Neal Lee

AU - Wang, Xiaoling

AU - Chen, Weiqin

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat dietinduced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose β3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning-induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counterregulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in AdmKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and β-adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance.

AB - Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat dietinduced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose β3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning-induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counterregulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in AdmKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and β-adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance.

KW - Adipose tissue

KW - Beta-oxidation

KW - Lipolysis and fatty acid metabolism

KW - Obesity

KW - Triglycerides

UR - http://www.scopus.com/inward/record.url?scp=84946558071&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946558071&partnerID=8YFLogxK

U2 - 10.1194/jlr.M060244

DO - 10.1194/jlr.M060244

M3 - Article

C2 - 26269358

AN - SCOPUS:84946558071

VL - 56

SP - 1912

EP - 1925

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 10

ER -