The Role of NAD+ in Metabolic Regulation of Adipose Tissue: Implications for Obesity-Induced Insulin Resistance

Tatjana Ruskovska; David A. Bernlohr

doi:10.3390/biomedicines11092560

The Role of NAD⁺ in Metabolic Regulation of Adipose Tissue: Implications for Obesity-Induced Insulin Resistance

Tatjana Ruskovska, David A. Bernlohr

Metabolic and Systems Biology (BMBB)

Research output: Contribution to journal › Review article › peer-review

1 Scopus citations

Abstract

Obesity-induced insulin resistance is among the key factors in the development of type 2 diabetes, atherogenic dyslipidemia and cardiovascular disease. Adipose tissue plays a key role in the regulation of whole-body metabolism and insulin sensitivity. In obesity, adipose tissue becomes inflamed and dysfunctional, exhibiting a modified biochemical signature and adipokine secretion pattern that promotes insulin resistance in peripheral tissues. An important hallmark of dysfunctional obese adipose tissue is impaired NAD⁺/sirtuin signaling. In this chapter, we summarize the evidence for impairment of the NAD⁺/sirtuin pathway in obesity, not only in white adipose tissue but also in brown adipose tissue and during the process of beiging, together with correlative evidence from human studies. We also describe the role of PARPs and CD38 as important NAD⁺ consumers and discuss findings from experimental studies that investigated potential NAD⁺ boosting strategies and their efficacy in restoring impaired NAD⁺ metabolism in dysfunctional obese adipose tissue. In sum, these studies suggest a critical role of NAD⁺ metabolism in adipose biology and provide a basis for the potential development of strategies to restore metabolic health in obesity.

Original language	English (US)
Article number	2560
Journal	Biomedicines
Volume	11
Issue number	9
DOIs	https://doi.org/10.3390/biomedicines11092560
State	Published - Sep 2023

Bibliographical note

Funding Information:
This research was funded by NIH R01 DK053189 to D.A.B. and by a Fulbright Fellowship award to T.R.

Funding Information:
T.R. was supported by the Fulbright grant No. 68140160, 2014/15, at the Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, USA. The authors thank Aleksandar Cvetkovski, Goce Delcev University—Stip, for his help in drawing the chemical structures used for the preparation of the figures and Timothy Walseth, University of Minnesota, for conducting NAD analysis. +

Publisher Copyright:
© 2023 by the authors.

Keywords

CD38
nicotinamide
nicotinamide mononucleotide
nicotinamide riboside
PARP
sirtuin
type 2 diabetes

PubMed: MeSH publication types

Journal Article
Review

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.3390/biomedicines11092560

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title = "The Role of NAD+ in Metabolic Regulation of Adipose Tissue: Implications for Obesity-Induced Insulin Resistance",

abstract = "Obesity-induced insulin resistance is among the key factors in the development of type 2 diabetes, atherogenic dyslipidemia and cardiovascular disease. Adipose tissue plays a key role in the regulation of whole-body metabolism and insulin sensitivity. In obesity, adipose tissue becomes inflamed and dysfunctional, exhibiting a modified biochemical signature and adipokine secretion pattern that promotes insulin resistance in peripheral tissues. An important hallmark of dysfunctional obese adipose tissue is impaired NAD+/sirtuin signaling. In this chapter, we summarize the evidence for impairment of the NAD+/sirtuin pathway in obesity, not only in white adipose tissue but also in brown adipose tissue and during the process of beiging, together with correlative evidence from human studies. We also describe the role of PARPs and CD38 as important NAD+ consumers and discuss findings from experimental studies that investigated potential NAD+ boosting strategies and their efficacy in restoring impaired NAD+ metabolism in dysfunctional obese adipose tissue. In sum, these studies suggest a critical role of NAD+ metabolism in adipose biology and provide a basis for the potential development of strategies to restore metabolic health in obesity.",

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author = "Tatjana Ruskovska and Bernlohr, {David A.}",

note = "Funding Information: This research was funded by NIH R01 DK053189 to D.A.B. and by a Fulbright Fellowship award to T.R. Funding Information: T.R. was supported by the Fulbright grant No. 68140160, 2014/15, at the Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, USA. The authors thank Aleksandar Cvetkovski, Goce Delcev University—Stip, for his help in drawing the chemical structures used for the preparation of the figures and Timothy Walseth, University of Minnesota, for conducting NAD analysis. + Publisher Copyright: {\textcopyright} 2023 by the authors.",

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N1 - Funding Information: This research was funded by NIH R01 DK053189 to D.A.B. and by a Fulbright Fellowship award to T.R. Funding Information: T.R. was supported by the Fulbright grant No. 68140160, 2014/15, at the Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, USA. The authors thank Aleksandar Cvetkovski, Goce Delcev University—Stip, for his help in drawing the chemical structures used for the preparation of the figures and Timothy Walseth, University of Minnesota, for conducting NAD analysis. + Publisher Copyright: © 2023 by the authors.

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N2 - Obesity-induced insulin resistance is among the key factors in the development of type 2 diabetes, atherogenic dyslipidemia and cardiovascular disease. Adipose tissue plays a key role in the regulation of whole-body metabolism and insulin sensitivity. In obesity, adipose tissue becomes inflamed and dysfunctional, exhibiting a modified biochemical signature and adipokine secretion pattern that promotes insulin resistance in peripheral tissues. An important hallmark of dysfunctional obese adipose tissue is impaired NAD+/sirtuin signaling. In this chapter, we summarize the evidence for impairment of the NAD+/sirtuin pathway in obesity, not only in white adipose tissue but also in brown adipose tissue and during the process of beiging, together with correlative evidence from human studies. We also describe the role of PARPs and CD38 as important NAD+ consumers and discuss findings from experimental studies that investigated potential NAD+ boosting strategies and their efficacy in restoring impaired NAD+ metabolism in dysfunctional obese adipose tissue. In sum, these studies suggest a critical role of NAD+ metabolism in adipose biology and provide a basis for the potential development of strategies to restore metabolic health in obesity.

AB - Obesity-induced insulin resistance is among the key factors in the development of type 2 diabetes, atherogenic dyslipidemia and cardiovascular disease. Adipose tissue plays a key role in the regulation of whole-body metabolism and insulin sensitivity. In obesity, adipose tissue becomes inflamed and dysfunctional, exhibiting a modified biochemical signature and adipokine secretion pattern that promotes insulin resistance in peripheral tissues. An important hallmark of dysfunctional obese adipose tissue is impaired NAD+/sirtuin signaling. In this chapter, we summarize the evidence for impairment of the NAD+/sirtuin pathway in obesity, not only in white adipose tissue but also in brown adipose tissue and during the process of beiging, together with correlative evidence from human studies. We also describe the role of PARPs and CD38 as important NAD+ consumers and discuss findings from experimental studies that investigated potential NAD+ boosting strategies and their efficacy in restoring impaired NAD+ metabolism in dysfunctional obese adipose tissue. In sum, these studies suggest a critical role of NAD+ metabolism in adipose biology and provide a basis for the potential development of strategies to restore metabolic health in obesity.

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