Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning

Michael D. Neinast, Aaron P. Frank, Juliet F. Zechner, Quanlin Li, Lavanya Vishvanath, Biff F Palmer, Vincent Aguirre, Rana K Gupta, Deborah J. Clegg

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35 Citations (Scopus)

Abstract

Objective: Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These 'BRITE/beige' adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as "browning." Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. Methods: Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. Results: RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. β3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:. Npr3 and Npr2:. Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. Conclusions: Upregulation of Nppb, Npr1, Npr2, and β3-. adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive effect of RYGB on metabolic parameters and may in part be mediated through upregulation of natriuretic peptides.

Original languageEnglish (US)
Pages (from-to)427-436
Number of pages10
JournalMolecular Metabolism
Volume4
Issue number5
DOIs
StatePublished - 2015

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Natriuretic Peptides
Gastric Bypass
Sympathetic Nervous System
Adipose Tissue
White Adipose Tissue
Homeostasis
Peptide Receptors
Adipocytes
Glucose
Adrenergic Receptors
Weight Loss
Up-Regulation
Brown Adipocytes
Weights and Measures
Brain Natriuretic Peptide
Atrial Natriuretic Factor
Type 2 Diabetes Mellitus
Obesity
Eating
Fats

Keywords

  • Atrial natriuretic peptide (ANP)
  • B-type natriuretic peptide (BNP)
  • Browning
  • High fat diet (HFD)
  • Natriuretic peptide receptor
  • Roux-en-Y gastric bypass (RYGB)

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning. / Neinast, Michael D.; Frank, Aaron P.; Zechner, Juliet F.; Li, Quanlin; Vishvanath, Lavanya; Palmer, Biff F; Aguirre, Vincent; Gupta, Rana K; Clegg, Deborah J.

In: Molecular Metabolism, Vol. 4, No. 5, 2015, p. 427-436.

Research output: Contribution to journalArticle

Neinast, Michael D. ; Frank, Aaron P. ; Zechner, Juliet F. ; Li, Quanlin ; Vishvanath, Lavanya ; Palmer, Biff F ; Aguirre, Vincent ; Gupta, Rana K ; Clegg, Deborah J. / Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning. In: Molecular Metabolism. 2015 ; Vol. 4, No. 5. pp. 427-436.
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abstract = "Objective: Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These 'BRITE/beige' adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as {"}browning.{"} Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. Methods: Wild type, female, C57/Bl6 mice were fed a 60{\%} fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. Results: RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. β3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:. Npr3 and Npr2:. Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. Conclusions: Upregulation of Nppb, Npr1, Npr2, and β3-. adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive effect of RYGB on metabolic parameters and may in part be mediated through upregulation of natriuretic peptides.",
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AU - Frank, Aaron P.

AU - Zechner, Juliet F.

AU - Li, Quanlin

AU - Vishvanath, Lavanya

AU - Palmer, Biff F

AU - Aguirre, Vincent

AU - Gupta, Rana K

AU - Clegg, Deborah J.

PY - 2015

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N2 - Objective: Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These 'BRITE/beige' adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as "browning." Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. Methods: Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. Results: RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. β3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:. Npr3 and Npr2:. Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. Conclusions: Upregulation of Nppb, Npr1, Npr2, and β3-. adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive effect of RYGB on metabolic parameters and may in part be mediated through upregulation of natriuretic peptides.

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KW - Roux-en-Y gastric bypass (RYGB)

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