Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death. This phenotype is aggravated and additional NAFLD features are differentially induced in apoCIII mice fed a HFD. HFD induced glucose intolerance together with increased gluconeogenesis, indicating hepatic insulin resistance. Additionally, the HFD led to marked increases in plasma TNFα (8-fold) and IL-6 (60%) in apoCIII mice. Cell death signaling (Bax/Bcl2), effector (caspase-3), and apoptosis were augmented in apoCIII mice regardless of whether a HFD or a low-fat diet was provided. Fenofibrate treatment reversed several of the effects associated with diet and apoCIII expression but did not normalize inflammatory traits even when liver lipid content was fully corrected. These results indicate that apoCIII and/or hypertriglyceridemia plays a major role in liver inflammation and cell death, which in turn increases susceptibility to and the severity of diet-induced NAFLD.

Endothelial dysfunction precedes atherosclerosis and is an independent predictor of cardiovascular events. Cholesterol levels and oxidative stress are key contributors to endothelial damage, whereas high levels of plasma high-density lipoproteins (HDL) could prevent it. Cholesteryl ester transfer protein (CETP) is one of the most potent endogenous negative regulators of HDL-cholesterol. However, whether and to what degree CETP expression impacts endothelial function, and the molecular mechanisms underlying the vascular effects of CETP on endothelial cells, have not been addressed. Acetylcholine-induced endothelium-dependent relaxation of aortic rings was impaired in human CETP-expressing transgenic mice, compared to their non-transgenic littermates. However, endothelial nitric oxide synthase (eNOS) activation was enhanced. The generation of superoxide and hydrogen peroxide was increased in aortas from CETP transgenic mice, while silencing CETP in cultured human aortic endothelial cells effectively decreased oxidative stress promoted by all major sources of ROS: mitochondria and NOX2. The endoplasmic reticulum stress markers, known as GADD153, PERK, and ARF6, and unfolded protein response effectors, were also diminished. Silencing CETP reduced endothelial tumor necrosis factor (TNF) α levels, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expression, diminishing monocyte adhesion. These results support the notion that CETP expression negatively impacts endothelial cell function, revealing a new mechanism that might contribute to atherosclerosis.

Diana Borges DOCK-NASCIMENTO 1 R E S U M O ObjetivoCorrelacionar a incidência de úlcera por pressão com o estado nutricional e a capacidade funcional de pacientes internados. MétodosEstudo de corte transversal realizado em dois hospitais, totalizando 130 pacientes (idade mediana = 52 (14-85) anos, 77 (59,2%) homens e 53 (40,8%) mulheres), sendo 72 (55,4%) internados para tratamento clínico, 40 (30,8%) para tratamento cirúrgico e 18 (13,8%) em terapia intensiva. Os pacientes foram avaliados pela avaliação subjetiva global e classificados, de acordo com sua capacidade funcional, em acamados e não acamados. Registrou-se a presença e número de úlceras, e sua gravidade. A classificação das úlceras foi estabelecida como grave, para lesões de 3º e 4º graus, e leve, para os graus 1 e 2. ResultadosA incidência de úlcera por pressão na população estudada foi de 19,2% (n=25). Não houve associação significativa com o sexo, a idade e tipo de tratamento do paciente. Os pacientes acamados apresentaram 7,5 vezes mais chance de apresentar úlceras (19/50; 38,0%) do que os que deambulavam (6/80; 7,5%; OR=7,5;

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.

Nutritional recovery with a soyabean diet decreases body and fat weights when compared with a casein diet. We investigated whether the reduced adiposity observed in rats recovering from early-life malnutrition with a soyabean diet results from alterations in lipid metabolism in white adipose tissue (WAT) and/or brown adipose tissue (BAT). Male rats from mothers fed either 17 or 6 % protein during pregnancy and lactation were maintained on 17 % casein (CC and LC groups), 17 % soyabean (CS and LS groups) or 6 % casein (LL group) diets over 60 d. The rats maintained on a soyabean diet had similar relative food intakes, but lower body and retroperitoneal WAT weights and a reduced lipid content in the retroperitoneal WAT. The insulin levels were lower in the recovered rats and were elevated in those fed a soyabean diet. Serum T3 concentration and uncoupling protein 1 content in the BAT were decreased in the recovered rats. The thermogenic capacity of the BAT was not affected by the soyabean diet. The lipogenesis rate in the retroperitoneal WAT was similar in all of the groups except for the LL group, which had exacerbated lipogenesis. The enhancement of the lipolysis rate by isoproterenol was decreased in white adipocytes from the soyabean-recovered rats and was elevated in adipocytes from the soyabean-control rats. Thus, in animals maintained on a soyabean diet, the proportions of fat deposits are determined by the lipolysis rate, which differs depending on the previous nutritional status. Key words: Nutritional recovery: Soyabean diet: Adipose tissue: RatsSoya-containing diets have been shown to alter several parameters involved in maintaining body homeostasis, energy expenditure and feeding behaviour (1 -3) . Soya protein and isoflavone have been reported to reduce fat-pad weight by increasing uncoupling protein 1 (UCP-1) expression in brown adipose tissue (BAT) (4) . UCP-1 is a molecule that uncouples mitochondrial oxidative phosphorylation by bypassing the electrochemical gradient across the inner membrane from * Corresponding author: M. S. F. Martins, fax þ55 65 3615 8811, email msfm.cba@gmail.com Abbreviations: BAT, brown adipose tissue; C, control; CC, offspring born to and suckled by mothers fed a control diet that were fed a control diet after weaning; CS, offspring born to and suckled by mothers fed a control diet that were fed a soyabean diet with 17 % protein after weaning; HOMA-IR, homeostasis model assessment of insulin resistance; LC, offspring of mothers fed a low-protein diet that were fed a control diet after weaning; LL, offspring of mothers fed a low-protein diet that were fed a low-protein diet after weaning; LP, low-protein; LS, offspring of mothers fed a low-protein diet that were fed a soyabean diet containing 17 % protein after weaning; RWAT, retroperitoneal white adipose tissue; Tris, 2-amino-2-hydroxymethyl-propane-1,3-diol; UCP-1, uncoupling protein 1; WAT, white adipose tissue.