Apolipoprotein CIII overexpression exacerbates diet-induced obesity due to adipose tissue higher exogenous lipid uptake and retention and lower lipolysis rates

Abstract

BackgroundHypertriglyceridemia is a common type of dyslipidemia found in obesity. However, it is not established whether primary hyperlipidemia can predispose to obesity. Evidences have suggested that proteins primarily related to plasma lipoprotein transport, such as apolipoprotein (apo) CIII and E, may significantly affect the process of body fat accumulation. We have previously observed an increased adiposity in response to a high fat diet (HFD) in mice overexpressing apoCIII. Here, we examined the potential mechanisms involved in this exacerbated response of apoCIII mice to the HFD.MethodsWe measured body energy balance, tissue capacity to store exogenous lipids, lipogenesis and lipolysis rates in non-transgenic and apoCIII overexpressing mice fed a HFD during two months.ResultsFood intake, fat excretion and whole body CO2 production were similar in both groups. However, the adipose tissue mass (45 %) and leptin plasma levels (2-fold) were significantly greater in apoCIII mice. Lipogenesis rates were similar, while exogenous lipid retention was increased in perigonadal (2-fold) and brown adipose tissues (40 %) of apoCIII mice. In addition, adipocyte basal lipolysis (55 %) and in vivo lipolysis index (30 %) were significantly decreased in apoCIII mice. A fat tolerance test evidenced delayed plasma triglyceride clearance and greater transient availability of non-esterified fatty acids (NEFA) during the post-prandial state in the apoCIII mice plasma. Thus, apoCIII overexpression resulted in increased NEFA availability to adipose uptake and decreased adipocyte lipolysis, favoring lipid enlargement of adipose depots.ConclusionWe propose that plasma apoCIII levels represent a new risk factor for diet-induced obesity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-015-0058-6) contains supplementary material, which is available to authorized users.

Apolipoprotein CIII Overexpression‐Induced Hypertriglyceridemia Increases Nonalcoholic Fatty Liver Disease in Association with Inflammation and Cell Death

“…Here, we confirmed that HFD consumption induces insulin resistance more severely in apoCIII mice than in NTg mice, as shown by the simultaneous glucose intolerance and increased gluconeogenesis that developed in the former group. We also confirmed a recent find from our group that apoCIII overexpression aggravates diet-induced obesity [26]. We have previously shown that apoCIII mice exhibit normal glucose homeostasis and insulin secretion when fed a normal diet, and these parameters were disturbed following acute increases in plasma FFA levels induced by heparin [27] or HFD consumption [28].…”

Novel role of cholesteryl ester transfer protein (CETP): attenuation of adiposity by enhancing lipolysis and brown adipose tissue activity

“…Numerous genes have been shown to modulate adiposity during recent decades. Among them, genes encoding proteins primarily related to plasma lipoprotein transport have been associated with body fat accumulation, such as apolipoprotein (apo) CIII and apo E [13][14][15][16]. In a previous work, we demonstrated that CETP expression attenuated diet-induced obesity in hypertriglyceridemic apo CIII-overexpressing mice [17].…”

Microbial lipases and their industrial applications: a comprehensive review

“…Diet encouraged over-expression of human LPL hinders the diet-induced obesity in the skeletal muscles of transgenic mice [ 614 , 615 ]. The ratio of carbohydrate: fat oxidation remains unperturbed indicated in the observation of constant Respiratory Quotient (RQ; moles of CO 2 production per mole of Oxygen consumed) [ 616 ]. A relationship between the RQ and body weight revealed in previously published analysis.…”