Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.
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.
Kumar
K Ganesh
KG
Neuropeptides Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Trevaskis
James L
JL
Lam
Daniel D
DD
Sutton
Gregory M
GM
Koza
Robert A
RA
Chouljenko
Vladimir N
VN
Kousoulas
Konstantin G
KG
Rogers
Pamela M
PM
Kesterson
Robert A
RA
Thearle
Marie
M
Ferrante
Anthony W
AW
Mynatt
Randall L
RL
Burris
Thomas P
TP
Dong
Jesse Z
JZ
Halem
Heather A
HA
Culler
Michael D
MD
Heisler
Lora K
LK
Stephens
Jacqueline M
JM
Butler
Andrew A
AA
D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001565:Benzoates / Q000737:chemistry / Q000378:metabolism; D001596:Benzylamines / Q000737:chemistry / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000819:agonists / Q000378:metabolism; D004734:Energy Metabolism; D005215:Fasting; D005234:Fatty Liver / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D010455:Peptides; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism
D001565:Benzoates; D001596:Benzylamines; D001798:Blood Proteins; D004268:DNA-Binding Proteins; C568440:Enho protein, human; C534289:Enho protein, mouse; C473027:GW 3965; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear