Contribution of Hepatic Retinaldehyde Dehydrogenase Induction to Impairment of Glucose Metabolism by High‐Fat‐Diet Feeding in C57BL/6J Mice

Abstract

Obesity and insulin resistance are associated with overexpression of retinaldehyde dehydrogenase 1 (RALDH1). We aimed to investigate the roles of hepatic RALDH1 induction in glucose metabolism impairment using mice fed with high-fat-diet (HFD). Mice were fed with HFD for 8 weeks and treated with RALDH inhibitor citral for another 4 weeks. Oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT) and insulin tolerance test were performed. Expressions of phosphoenolpyruvate carboxykinase 1 (PCK1), glucokinase (GCK) and RALDH1 were measured. Therapeutic effects of citral were also documented in diabetic rats. Effects of retinaldehyde on PCK1 and GCK expressions were examined in rat primary hepatocytes and HepG2 cells. The results showed that HFD mice were characterized by hyperlipidaemia and insulin resistance, accompanied by significantly increased RALDH1 activity and expression. Citral (10 and 50 mg/kg) ameliorated HFD-induced hyperlipidaemia and insulin resistance, as demonstrated by the improved fasting glucose, insulin levels and lipid profiles. OGTT and PTT demonstrated that citral reversed HFD-induced glucose disposal impairment and glucose production enhancement. Citral also reversed the increased PCK1 expression and decreased GCK expression by HFD. Citral therapeutic effects were reconfirmed in diabetic rats. In vitro data indicated that retinaldehyde had the strongest PCK1 induction in primary hepatocytes of diabetic rats compared with HFD rats and control rats, in line with the increased RALDH1 expression. Citral reversed the retinaldehyde-induced PCK1 expression in primary rat hepatocytes and HepG2 cells. In conclusion, RALDH1 induction impaired glucose metabolism partly via modulating PCK1 and GCK expressions. Citral improved glucose metabolism through inhibiting RALDH activity.

Dietary citral increase growth and health performance of shrimp Penaeus vannamei

“…Immune system includes detect pathogen, phagocytic activity, cytotoxicity, encapsulation, wound healing, and proPO activation (Xu et al, 2018). The result of this study showed that THC in shrimp reared with the addition of citral treatment in feed was higher than control.…”

“…This is thought to be caused by two things, the first is an inhibition in glucose absorption process from intestine into the blood or the second is an increase in the rate of blood glucose absorption into the liver tissue or other organ. The previous study in rat showed that citral could decrease blood glucose level and increase insulin plasma concentration in diabetic rat (Mishra et al, 2019;Xu et al, 2018). Xu et al, 2018 showed that therapeutic effect of citral in glucose metabolism associated with the increase of insulin sensitivity and the decrease of endogenous glucose production in diabetic rat, furthermorem citral concentration influenced these effects.…”

“…The previous study in rat showed that citral could decrease blood glucose level and increase insulin plasma concentration in diabetic rat (Mishra et al, 2019;Xu et al, 2018). Xu et al, 2018 showed that therapeutic effect of citral in glucose metabolism associated with the increase of insulin sensitivity and the decrease of endogenous glucose production in diabetic rat, furthermorem citral concentration influenced these effects. Some of secondary metabolite in citral such as tannins, steroids, and also triterpenoids are able to accelerate glucose absorption process in the blood.…”

Identifying candidate reference chemicals for in vitro testing of the retinoid pathway for predictive developmental toxicity

“…The natural product citral has been known for many years to be an aldehyde dehydrogenase inhibitor, and it has routinely been used to block ATRA synthesis in the laboratory ( Xu et al, 2018 ; Kikonyogo et al, 1999 ).…”

The use of isotretinoin in acne therapy in early childhood and its effect on the occurrence of acne symptoms later in life. Eight-year follow-up

“…The levels then stabilize and return to normal within 8 weeks after treatment is stopped. Therapy should be stopped if the triglyceride level exceeds 8.0 mmol/l because of a risk of pancreatitis [16]. More dramatic increases in the triglyceride level have been observed in patients who were obese, consumed excessive amounts of alcohol, had a family history of hyperlipidaemia or other risk factors [17].…”