Upregulation of Lipogenesis and Protein Tyrosine Phosphatase-1B Expression in the Liver of Wistar Rats with Metabolic Syndrome Chronically Induced by Drinking Sucrose Water

Abstract

Background: Establishing animal models with metabolic disorders similar to human metabolic syndrome (MS) is important. In terms of eliciting a full array of MS, we have previously shown that Wistar rats are more responsive to sucrose water drinking than are C57BL/6J mice. This study was aimed at investigating the underlying molecular mechanism of sucrose water-induced MS in Wistar rats. Methods: Male Wistar rats were divided into 2 groups (n = 8 for each group) which were given plain water (C group) or 30% sucrose water (SW group) to drink ad libitum. After 20 weeks, the transcriptional levels and protein translocation of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate response element-binding protein (ChREBP) as well as the protein levels of protein tyrosine phosphatase-1B (PTP-1B) in insulin-responsive tissues (liver, muscle, and adipose tissue) were measured. Results: The sucrose water regimen successfully elicited visceral obesity, hypertriglyceridemia, insulin resistance, and high blood pressure. The upregulation of de novo lipogenesis in the liver of the sucrose water-treated rats was demonstrated by an increased activity of enzymes, mRNA levels of lipogenic proteins, and nuclear levels of SREBP-1c and ChREBP. Moreover, in the sucrose water-treated rats, protein levels of PTP-1B were significantly increased in liver and skeletal muscle but decreased in adipose tissue. Conclusion: The susceptibility of Wistar rats to sucrose water-induced MS is associated with the transactivation of SREBP-1c and ChREBP in the liver, and PTP-1B is involved in the upregulation of de novo lipogenesis in the liver and the pathology of systemic insulin resistance in rats with MS chronically induced by drinking sucrose water.

Mechanisms by which the thiazolidinedione troglitazone protects against sucrose‐induced hepatic fat accumulation and hyperinsulinaemia

“…Total epididymal adipose tissue triglyceride content was not different between SC and HS‐C (Table ). However, in agreement with earlier studies (Huang et al ., ), hepatic triglyceride levels were threefold higher in HS‐C compared with SC (Figure ). Moreover, fractional DNL rates (Figure ) were increased approximately twofold in HS‐C‐fed compared with SC‐fed rats.…”

Energy restriction does not prevent insulin resistance but does prevent liver steatosis in aging rats on a Western-style diet

“…The fructose component of sucrose increases hepatic de novo lipogenesis and TG synthesis [36,37] and, thus may have exacerbated the age-related TG accumulation observed in liver [38], skeletal muscle [39], and plasma [39,40]. In plasma, higher plasma TC and cholesteryl ester concentrations in 19 AL rats are probably associated with the increase in hepatic cholesterol synthesis and reduced clearance of plasma low-density lipoprotein observed during aging [41,42] and u-3 PUFA deficiency [43].…”