Adropin Deficiency Is Associated With Increased Adiposity and Insulin Resistance

Abstract

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 (EndoRa) 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.

Regulation of Substrate Oxidation Preferences in Muscle by the Peptide Hormone Adropin

“…Whole-body AdrKO and AdrTG on a C57BL/6J (B6) background were described previously (1,2). Wild-type (WT) B6 mice were purchased from The Jackson Laboratory (Bar Harbor, ME).…”

Adropin induction of lipoprotein lipase expression in tilapia hepatocytes

“…Transgenic over expression or systemic adropin treatments markedly attenuate insulin resistance and glucose intolerance in diet-induced obese mice (Kumar et al 2008). In line with these observations, adropin knockout mice were associated with increased hepatosteatosis, adiposity and insulin resistance (Ganesh Kumar et al 2012). Even though the linkage between circulating adropin levels and other various pathophysiological conditions in mammals have been reported, the exact link with adropin remains elusive.…”

“…Besides, adropin may be involved in the metabolic adaptation to fasting, although these data are still controversial. In fasting mice, adropin expression is attenuated compared with control values (Kumar et al 2008), whereas plasma adropin levels in humans do not change in response to fasting (Ganesh Kumar et al 2012). Unlike its mammalian counterparts, the physiological significance of adropin is still poorly understood in fish.…”

Postnatal Prevention of Childhood Obesity in Offspring Prenatally Exposed to Gestational Diabetes mellitus: Where Are We Now

“…Adropin is a peptide hormone, encoded by the energy homeostasis-associated gene ( Enho ) that is involved in the regulation of metabolic homeostasis in mice [45,46]. Aydin et al [47] found that women with GDM had lower adropin concentrations in their colostrum than women without GDM, but that adropin levels were not different in transitional (7 days postpartum) and mature milk between groups.…”

“…Aydin et al [47] found that women with GDM had lower adropin concentrations in their colostrum than women without GDM, but that adropin levels were not different in transitional (7 days postpartum) and mature milk between groups. It has been demonstrated that adropin deficiency is associated with higher body fat mass in mice, suggesting that being exposed to lower levels of adropin from GDMBM may also lead to an increased body fat mass in children , as in mice [46]. Furthermore, irisin is a myokine involved in thermogenesis by inducing conversion of white adipose tissue into brown adipose tissue [48].…”