Short and Long-Term Impact of Lipectomy on Expression Profile of Hepatic Anabolic Genes in Rats: A High Fat and High Cholesterol Diet-Induced Obese Model

Abstract

ObjectiveTo understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats.MethodsThe hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR) ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined.ResultsNo significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α) and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC) analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, P<0.05) and negatively to glucose and insulin (r = −0.821 and −0.892 respectively, P<0.05). Eight weeks after the operation, the lipectomized animals revealed significant higher body and liver weights, weight gain, liver to body weight ratio, hepatic triacylglycerol and serum insulin level.ConclusionsIn response to lipectomy a short term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These metabolic changes could be the results of reduced circulating adiponectin that further influences the functions of insulin and hepatic HNF4α.

Up-Regulation Mttp and Apob Gene Expression in Rat Liver is Related to Post-Lipectomy Hypertriglyceridemia

“…Taking into account the results of previous studies in which HNF1α and HNF4α were shown to be transcriptional activators of Mttp and Apob genes [38,39], and our hereby presented findings, we postulate that these hepatocyte nuclear factors (HNFs) might contribute to the hypertriglyceridemia observed in lipectomized rats. This is consistent with the results of a recent study in which lipectomized rats presented with higher concentrations of circulating TAGs and higher liver levels of HNF4α mRNA than the sham-operated controls [13]. Further evidence supporting a role of HNFs in the post-lipectomy increase in serum TAGs comes from a study of Mttp and Apob expressions and serum TAG concentrations in mice lacking liver Hnf4a ; these animals presented with significantly lower serum concentrations of TAGs [40].…”

“…Recently, Ling et al [13] reported that lipectomy results in an increase in serum TAG concentration and up-regulation of liver genes encoding proteins involved in lipid metabolism in rats. They suggested that lower serum concentration of adiponectin may contribute to the post-lipectomy hyperlipidemia [13].…”

“…They suggested that lower serum concentration of adiponectin may contribute to the post-lipectomy hyperlipidemia [13]. Interestingly, elevated level of serum TAGs was also reported in transgenic mice (A-ZIP/F-1 mice) lacking white adipose tissue (WAT) [14].…”

Up-regulation of orexigenic and down-regulation of anorexigenic neuropeptide gene expression in rat hypothalamus after partial lipectomy

“…The postlipectomy increase in food intake can be explained by the fact, that NPY and AgRP are the most potent known orexigenic neuropeptides, whereas POMC and CART are considered the most potent anorexigenic neuropeptides. However, contrary to our findings, several previous studies showed no effect of lipectomy on food intake in mice with genetic alterations of leptin and its receptor (Harris et al, 2002), Siberian hamster (Shi and Bartness, 2005) and rats (Ling et al, 2014;Bueno et al, 2011Bueno et al, , 2005. One possible explanation for these discrepancies is a different effect of lipectomy on circulating leptin concentration.…”

“…One possible explanation for these discrepancies is a different effect of lipectomy on circulating leptin concentration. We found a significant post-lipectomy decrease in circulating leptin concentration, whereas other authors showed that lipectomy exerts no effect on this parameter (Ling et al, 2014;Bueno et al, 2011). Too small amount of removed WAT may be one reason behind the lack of post-lipectomy changes in circulating leptin concentration and, consequently, food intake.…”