Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism

K. Ganesh Kumar; James L. Trevaskis; Daniel D. Lam; Gregory M. Sutton; Robert A. Koza; Vladimir N. Chouljenko; Konstantin G. Kousoulas; Pamela M. Rogers; Robert A. Kesterson; Marie Thearle; Anthony W. Ferrante; Randall L. Mynatt; Thomas P. Burris; Jesse Z. Dong; Heather A. Halem; Michael D. Culler; Lora K. Heisler; Jacqueline M. Stephens; Andrew A. Butler

doi:10.1016/j.cmet.2008.10.011

Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism

K. Ganesh Kumar
, James L. Trevaskis
, Daniel D. Lam
, Gregory M. Sutton
, Robert A. Koza
, Vladimir N. Chouljenko
, Konstantin G. Kousoulas
, Pamela M. Rogers
, Robert A. Kesterson
, Marie Thearle
, Anthony W. Ferrante
, Randall L. Mynatt
, Thomas P. Burris
, Jesse Z. Dong
, Heather A. Halem
, Michael D. Culler
, Lora K. Heisler
, Jacqueline M. Stephens
, Andrew A. Butler^*

^*Corresponding author for this work

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

427 Citations (Scopus)

Abstract

Obesity and nutrient homeostasis are linked by mechanisms that are not fully elucidated. Here we describe a secreted protein, adropin, encoded by a gene, Energy Homeostasis Associated (Enho), expressed in liver and brain. Liver Enho expression is regulated by nutrition: lean C57BL/6J mice fed high-fat diet (HFD) exhibited a rapid increase, while fasting reduced expression compared to controls. However, liver Enho expression declines with diet-induced obesity (DIO) associated with 3 months of HFD or with genetically induced obesity, suggesting an association with metabolic disorders in the obese state. In DIO mice, transgenic overexpression or systemic adropin treatment attenuated hepatosteatosis and insulin resistance independently of effects on adiposity or food intake. Adropin regulated expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor gamma, a major regulator of lipogenesis. Adropin may therefore be a factor governing glucose and lipid homeostasis, which protects against hepatosteatosis and hyperinsulinemia associated with obesity.

Original language	English
Pages (from-to)	468-481
Number of pages	14
Journal	Cell Metabolism
Volume	8
Issue number	6
Early online date	2 Dec 2008
DOIs	https://doi.org/10.1016/j.cmet.2008.10.011
Publication status	Published - 6 Dec 2008

Funding

This work was supported by grants from the Pennington Biomedical Research Foundation and the American Diabetes Association (1-04-JF09) and by a Sponsored Research Agreement with Biomeasure, Inc./IPSEN; Milford, MA to A.A.B. A.A.B. and R.L.M. are supported in part by CNRU Center Grant #1P30 DK072476, entitled "Nutritional Programming: Environmental and Molecular Interactions" and sponsored by the NIDDK. The UAB Transgenic Mouse Facility is supported by NIH grants P30 CA1 3148 and P30 AR48311. L.K.H. is supported by NIDDK R01DK065171 and the Wellcome Trust. H.A.H., J.Z.D., and M.D.C. are employees of Biomeasure, Inc./IPSEN; A.A.B. has been a paid consultant for Biomeasure, Inc.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

adipose-tissue
insulin-resistance
melanocortin system
food-intake
receptor
glucose
obesity
liver
mice
pathogenesis

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10.1016/j.cmet.2008.10.011Licence: Unspecified

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Kumar, K. G., Trevaskis, J. L., Lam, D. D., Sutton, G. M., Koza, R. A., Chouljenko, V. N., Kousoulas, K. G., Rogers, P. M., Kesterson, R. A., Thearle, M., Ferrante, A. W., Mynatt, R. L., Burris, T. P., Dong, J. Z., Halem, H. A., Culler, M. D., Heisler, L. K., Stephens, J. M., & Butler, A. A. (2008). Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metabolism, 8(6), 468-481. https://doi.org/10.1016/j.cmet.2008.10.011

Kumar, KG, Trevaskis, JL, Lam, DD, Sutton, GM, Koza, RA, Chouljenko, VN, Kousoulas, KG, Rogers, PM, Kesterson, RA, Thearle, M, Ferrante, AW, Mynatt, RL, Burris, TP, Dong, JZ, Halem, HA, Culler, MD, Heisler, LK, Stephens, JM & Butler, AA 2008, 'Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism', Cell Metabolism, vol. 8, no. 6, pp. 468-481. https://doi.org/10.1016/j.cmet.2008.10.011

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title = "Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism",

abstract = "Obesity and nutrient homeostasis are linked by mechanisms that are not fully elucidated. Here we describe a secreted protein, adropin, encoded by a gene, Energy Homeostasis Associated (Enho), expressed in liver and brain. Liver Enho expression is regulated by nutrition: lean C57BL/6J mice fed high-fat diet (HFD) exhibited a rapid increase, while fasting reduced expression compared to controls. However, liver Enho expression declines with diet-induced obesity (DIO) associated with 3 months of HFD or with genetically induced obesity, suggesting an association with metabolic disorders in the obese state. In DIO mice, transgenic overexpression or systemic adropin treatment attenuated hepatosteatosis and insulin resistance independently of effects on adiposity or food intake. Adropin regulated expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor gamma, a major regulator of lipogenesis. Adropin may therefore be a factor governing glucose and lipid homeostasis, which protects against hepatosteatosis and hyperinsulinemia associated with obesity.",

keywords = "adipose-tissue, insulin-resistance, melanocortin system, food-intake, receptor, glucose, obesity , liver, mice, pathogenesis",

author = "Kumar, \{K. Ganesh\} and Trevaskis, \{James L.\} and Lam, \{Daniel D.\} and Sutton, \{Gregory M.\} and Koza, \{Robert A.\} and Chouljenko, \{Vladimir N.\} and Kousoulas, \{Konstantin G.\} and Rogers, \{Pamela M.\} and Kesterson, \{Robert A.\} and Marie Thearle and Ferrante, \{Anthony W.\} and Mynatt, \{Randall L.\} and Burris, \{Thomas P.\} and Dong, \{Jesse Z.\} and Halem, \{Heather A.\} and Culler, \{Michael D.\} and Heisler, \{Lora K.\} and Stephens, \{Jacqueline M.\} and Butler, \{Andrew A.\}",

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AU - Kumar, K. Ganesh

AU - Trevaskis, James L.

AU - Lam, Daniel D.

AU - Sutton, Gregory M.

AU - Koza, Robert A.

AU - Chouljenko, Vladimir N.

AU - Kousoulas, Konstantin G.

AU - Rogers, Pamela M.

AU - Kesterson, Robert A.

AU - Thearle, Marie

AU - Ferrante, Anthony W.

AU - Mynatt, Randall L.

AU - Burris, Thomas P.

AU - Dong, Jesse Z.

AU - Halem, Heather A.

AU - Culler, Michael D.

AU - Heisler, Lora K.

AU - Stephens, Jacqueline M.

AU - Butler, Andrew A.

PY - 2008/12/6

Y1 - 2008/12/6

N2 - Obesity and nutrient homeostasis are linked by mechanisms that are not fully elucidated. Here we describe a secreted protein, adropin, encoded by a gene, Energy Homeostasis Associated (Enho), expressed in liver and brain. Liver Enho expression is regulated by nutrition: lean C57BL/6J mice fed high-fat diet (HFD) exhibited a rapid increase, while fasting reduced expression compared to controls. However, liver Enho expression declines with diet-induced obesity (DIO) associated with 3 months of HFD or with genetically induced obesity, suggesting an association with metabolic disorders in the obese state. In DIO mice, transgenic overexpression or systemic adropin treatment attenuated hepatosteatosis and insulin resistance independently of effects on adiposity or food intake. Adropin regulated expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor gamma, a major regulator of lipogenesis. Adropin may therefore be a factor governing glucose and lipid homeostasis, which protects against hepatosteatosis and hyperinsulinemia associated with obesity.

AB - Obesity and nutrient homeostasis are linked by mechanisms that are not fully elucidated. Here we describe a secreted protein, adropin, encoded by a gene, Energy Homeostasis Associated (Enho), expressed in liver and brain. Liver Enho expression is regulated by nutrition: lean C57BL/6J mice fed high-fat diet (HFD) exhibited a rapid increase, while fasting reduced expression compared to controls. However, liver Enho expression declines with diet-induced obesity (DIO) associated with 3 months of HFD or with genetically induced obesity, suggesting an association with metabolic disorders in the obese state. In DIO mice, transgenic overexpression or systemic adropin treatment attenuated hepatosteatosis and insulin resistance independently of effects on adiposity or food intake. Adropin regulated expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor gamma, a major regulator of lipogenesis. Adropin may therefore be a factor governing glucose and lipid homeostasis, which protects against hepatosteatosis and hyperinsulinemia associated with obesity.

KW - adipose-tissue

KW - insulin-resistance

KW - melanocortin system

KW - food-intake

KW - receptor

KW - glucose

KW - obesity

KW - liver

KW - mice

KW - pathogenesis

U2 - 10.1016/j.cmet.2008.10.011

DO - 10.1016/j.cmet.2008.10.011

M3 - Article

SN - 1550-4131

VL - 8

SP - 468

EP - 481

JO - Cell Metabolism

JF - Cell Metabolism

IS - 6

ER -

Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism

Abstract

Funding

UN SDGs

Keywords

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