Adropin deficiency is associated with increased adiposity and insulin resistance.
Adropin is a secreted peptide that improves hepatic steatosis and glucose homeostasis when administered to diet-induced obese mice. It is not clear if adropin is a peptide hormone regulated by signals of metabolic state. Moreover, the significance of a decline in adropin expression with obesity with respect to metabolic disease is also not clear. We investigated the regulation of serum adropin by metabolic status and diet. Serum adropin levels were high in chow-fed conditions and were suppressed by fasting and diet-induced obesity (DIO). High adropin levels were observed in mice fed a high-fat low carbohydrate diet, whereas lower levels were observed in mice fed a low-fat high carbohydrate diet. To investigate the role of adropin deficiency in metabolic homeostasis, we generated adropin knockout mice (AdrKO) on the C57BL/6J background. AdrKO displayed a 50%-increase in increase in adiposity, although food intake and energy expenditure were normal. AdrKO also exhibited dyslipidemia and impaired suppression of endogenous glucose production (EndoR(a)) in hyperinsulinemic-euglycemic clamp conditions, suggesting insulin resistance. While homo- and heterozygous carriers of the null adropin allele exhibited normal DIO relative to controls, impaired glucose tolerance associated with weight gain was more severe in both groups. In summary, adropin is a peptide hormone regulated by fasting and feeding. In fed conditions, adropin levels are regulated dietary macronutrients, and increase with dietary fat content. Adropin is not required for regulating food intake, however, its functions impact on adiposity and are involved in preventing insulin resistance, dyslipidemia, and impaired glucose tolerance.
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL, USA.
K
K
Ganesh Kumar
Jingying
J
Zhang
Su
S
Gao
Jari
J
Rossi
Owen P
OP
McGuinness
Heather H
HH
Halem
Michael D
MD
Culler
Randall L
RL
Mynatt
Andrew A
AA
Butler
D050154:Adiposity; D000818:Animals; D056444:Axonemal Dyneins / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D050171:Dyslipidemias / Q000378:metabolism; D004435:Eating; D004734:Energy Metabolism; D005215:Fasting / Q000097:blood; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; C534289:Enho protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D056444:Axonemal Dyneins; C550778:Dnaic1 protein, mouse