Liver fat metabolism, obesity and diabetes in Psammomys obesis

Defects in fat metabolism are central to the aetiology and pathogenesis of obesity and type II diabetes. The liver plays a central role in these disease states via its regulation of glucose and fat metabolism. In addition, accumulation of fat within the liver has been associated with changes in key pathways of carbohydrate and fat metabolism. However a number of questions remain. It is hypothesised that fat accumulation within the liver is a primary defect in the aetiology and pathogenesis of obesity and type II diabetes. Fat accumulating in the liver is the result of changes in the gene expression of key enzymes and proteins involved with fat uptake, fat transport, fat oxidation, fat re-esterification or storage and export of fat from the liver and these changes are regulated by key lipid responsive transcription factors. To study these questions Psammomys obesus was utilised. This polygenic rodent model of obesity and type II diabetes develops obesity and diabetes in a similar pattern to susceptible human populations. In addition dietary and environmental changes to Psammomys obesus were employed to create different states of energy balance, which allowed the regulation of liver fat gene expression to be examined. These investigations include: 1) Measurement of fat accumulation and fatty acid binding proteins in lean, obese and diabetic Psammomys obesus. 2) Characterisation of hepatic lipid enzymes, transport protein and lipid responsive transcription factor gene expression in lean, obese and diabetic Paammomys obesus. 3) The effect of acute and chronic energy restriction on hepatic lipid metabolism in Psammomys obesus. 4) The effect of sucrose feeding on the development of obesity and type II diabetes in Psammomys obesus. 5) The effect of nicotine treatment in lean and obese Psammomys obesus, 6) The effect of high dose leptin administration on hepatic fat metabolism in Psammomys obesus. The results of these studies demonstrated that fat accumulation within the liver was not a primary defect in the aetiology and pathogenesis of obesity and type II diabetes. Fat accumulating in the liver was not the result of changes in the gene expression of key enzymes and proteins involved in hepatic fat metabolism. However changes in the mRNA level of the transcription factors PPAR∝ and SREBP-1C was associated with the development of diabetes and the gene expression of these two transcription factors was associated with changes in diabetic status.

Body build : its influence on anthropometric measurements, fat distribution, body composition and carbohydrate metabolism

Examines the interrelationships between body build and body composition and carbohydrate and lipid metabolism in healthy young men and women. Results indicate that in women a low relative sitting height may be an early marker of susceptibility to abdominal obesity and its consequences, non insulin dependent diabetes and coronary heart disease.

PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle

Defective control of lipid metabolism leading to lipotoxicity causes insulin resistance in skeletal muscle, a major factor leading to diabetes. Here, we demonstrate that perilipin (PLIN) 5 is required to couple intramyocellular triacylglycerol lipolysis with the metabolic demand for fatty acids. PLIN5 ablation depleted triacylglycerol stores but increased sphingolipids including ceramide, hydroxylceramides and sphingomyelin. We generated perilipin 5 (Plin5)-/- mice to determine the functional significance of PLIN5 in metabolic control and insulin action. Loss of PLIN5 had no effect on body weight, feeding or adiposity but increased whole-body carbohydrate oxidation. Plin5-/- mice developed skeletal muscle insulin resistance, which was associated with ceramide accumulation. Liver insulin sensitivity was improved in Plin5-/- mice, indicating tissue-specific effects of PLIN5 on insulin action. We conclude that PLIN5 plays a critical role in coordinating skeletal muscle triacylglycerol metabolism, which impacts sphingolipid metabolism, and is requisite for the maintenance of skeletal muscle insulin action. © 2014 The Authors.

Algae in fish feed: performances and fatty acid metabolism in juvenile Atlantic Salmon

Algae are at the base of the aquatic food chain, producing the food resources that fish are adapted to consume. Previous studies have proven that the inclusion of small amounts (<10% of the diet) of algae in fish feed (aquafeed) resulted in positive effects in growth performance and feed utilisation efficiency. Marine algae have also been shown to possess functional activities, helping in the mediation of lipid metabolism, and therefore are increasingly studied in human and animal nutrition. The aim of this study was to assess the potentials of two commercially available algae derived products (dry algae meal), Verdemin (derived from Ulva ohnoi) and Rosamin (derived from diatom Entomoneis spp.) for their possible inclusion into diet of Atlantic Salmon (Salmo salar). Fish performances, feed efficiency, lipid metabolism and final product quality were assessed to investigated the potential of the two algae products (in isolation at two inclusion levels, 2.5% and 5%, or in combination), in experimental diets specifically formulated with low fish meal and fish oil content. The results indicate that inclusion of algae product Verdemin and Rosamin at level of 2.5 and 5.0% did not cause any major positive, nor negative, effect in Atlantic Salmon growth and feed efficiency. An increase in the omega-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) content in whole body of fish fed 5% Rosamin was observed.

Lipid abundance in zebrafish embryos is regulated by complementary actions of the endocannabinoid system and retinoic acid pathway

The endocannabinoid system (ECS) and retinoic acid (RA) signaling have been associated with influencing lipid metabolism. We hypothesized that modulation of these pathways could modify lipid abundance in developing vertebrates and that these pathways could have a combinatorial effect on lipid levels. Zebrafish embryos were exposed to chemical treatments altering the activity of the ECS and RA pathway. Embryos were stained with the neutral lipid dye Oil-Red-O (ORO) and underwent whole-mount in situ hybridization. Mouse 3T3-L1 fibroblasts were differentiated under exposure to RA modulating chemicals and subsequently stained with ORO and analyzed for gene expression by qRT-PCR. ECS activation and RA exposure increased lipid abundance and the expression of lipoprotein lipase. Additionally, RA treatment increased expression of CCAAT/enhancer binding protein alpha. Both ECS receptors and RA receptor subtypes were separately involved in modulating lipid abundance. Finally, increased ECS or RA activity ameliorated the reduced lipid abundance caused by peroxisome proliferator-activated receptor gamma (PPARγ) inhibition. Therefore, the ECS and RA pathway influence lipid abundance in zebrafish embryos and have an additive effect when treated simultaneously. Furthermore, we demonstrated that these pathways act downstream or independently of PPARγ to influence lipid levels. Our study shows for the first time that the RA and ECS pathways have additive function in lipid abundance during vertebrate development.

Arachidonic acid and eicosapentaenoic acid metabolism in juvenile Atlantic Salmon as affected by water temperature

Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature recorded a significantly increased feed intake, these results clearly suggested that at high, sub-optimal water temperature, fish metabolism attempted to increment its overall ARA status -the most bioactive LC-PUFA participating in the inflammatory response- by modulating the metabolic fate of dietary ARA (expressed as % of net intake), reducing its β-oxidation and favouring synthesis and deposition. This correlates also with results from other recent studies showing that both immune- and stress- responses in fish are up regulated in fish held at high temperatures. This is a novel and fundamental information that warrants industry and scientific attention, in consideration of the imminent increase in water temperatures, continuous expansion of aquaculture operations, resources utilisation in aquafeed and much needed seasonal/adaptive nutritional strategies.

Co-feeding of live feed and inert diet from first-feeding affects Artemia lipid digestibility and retention in Senegalese sole (Solea senegalensis) larvae

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Orange juice decreases low-density lipoprotein cholesterol in hypercholesterolemic subjects and improves lipid transfer to high-density lipoprotein in normal and hypercholesterolemic subjects

Orange juice (OJ) is regularly consumed worldwide, but its effects on plasma lipids have rarely been explored. This study hypothesized that consumption of OJ concentrate would improve lipid levels and lipid metabolism, which are important in high-density lipoprotein (HDL) function in normolipidemic (NC) and hypercholesterolemic (HCH) subjects. Fourteen HCH and 31 NC adults consumed 750 mL/day OJ concentrate (1:6 OJ/water) for 60 days. Eight control subjects did not consume OJ for 60 days. Plasma was collected before and on the last clay for biochemical analysis and an in vitro as

Abnormalities in apolipoprotein and lipid levels in an HIV-infected Brazilian population under different treatment profiles: the relevance of apolipoprotein E genotypes and immunological status

HIV infection is associated with disturbances in lipid metabolism due to a host's response mechanism and the current antiretroviral therapy. The pathological appearance and progression of atherosclerosis is dependent on the presence of injurious agents in the vascular endothelium and variations in different subsets of candidate genes. Therefore, the Hha I polymorphism in the apolipoprotein E gene was evaluated in addition to triglycerides, total cholesterol, very low-density lipoprotein (VLDL), LDL, high-density lipoprotein (HDL), and apolipoprotein (apo) Al, B and E levels in 86 Brazilian HIV-infected patients and 29 healthy controls. The allele frequency for apoE in the HIV-infected group and controls was in agreement with data on the Brazilian population. Dyslipidemia was observed in the HIV group and verified by increased levels of triglycerides, VLDL and apoE, and decreased levels of HDL and apoAl. The greatest abnormalities in these biochemical variables were shown in the HIV-infected individuals whose immune function was more compromised. The effect of the genetic variation at the APOE gene on biochemical variables was more pronounced in the HIV-infected individuals who carried the apoE2/3 genotype. The highly active antiretroviral therapy (HAART)-receiving group presented increased levels of total cholesterol and apoE. Dyslipidemia was a predictable consequence of HIV infection and the protease inhibitors intensified the increase in apoE values.

Evaluation of Glycemic and Lipid Profile of Offspring of Diabetic Wistar Rats Treated with Malpighia emarginata Juice

Knowing that maternal diabetes is related to hyperglycemia and fetal hyperinsulinemia, which affect the lipid metabolism, the aim of this study was to evaluate the effects of Malpighia emarginata (acerola) juice on the glycemic and lipid profile of offspring of diabetic and nondiabetic Wistar rats. The adult offspring of non-diabetic dams and of dams with severe streptozotocin-induced diabetes were divided into groups: G1, offspring (of control dams) treated with water, G2, offspring (of diabetic dams) treated with water, G3, male offspring (of control dams) treated with acerola juice, and G4, male offspring (of diabetic dams) treated with acerola juice. The offspring of diabetic dams treated with acerola juice showed significantly decreased levels of glucose, cholesterol, triglycerides, and increased HDL-c. The use of acerola juice is a potential strategy to aid in the prevention of DM and dyslipidemia and its complications or to act as an auxiliary in the treatment of these diseases.

Monosodium glutamate in standard and high-fiber diets: Metabolic syndrome and oxidative stress in rats

Objective: This study determined the effects of adding monosodium glutamate (MSG) to a standard diet and a fiber-enriched diet on glucose metabolism, lipid profile, and oxidative stress in rats. Methods: Male Wistar rats (65 ± 5 g, n = 8) were fed a standard diet (control), a standard diet supplemented with 100 g of MSG per kilogram of rat body weight, a diet rich in fiber, or a diet rich in fiber supplemented with 100 g of MSG per kilogram of body weight. After 45 d of treatment, sera were analyzed for concentrations of insulin, leptin, glucose, triacylglycerol, lipid hydroperoxide, and total antioxidant substances. A homeostasis model assessment index was estimated to characterize insulin resistance. Results: Voluntary food intake was higher and feed efficiency was lower in animals fed the standard diet supplemented with MSG than in those fed the control, fiber-enriched, or fiber- and MSG-enriched diet. The MSG group had metabolic dysfunction characterized by increased levels of glucose, triacylglycerol, insulin, leptin, and homeostasis model assessment index. The adverse effects of MSG were related to an imbalance between the oxidant and antioxidant systems. The MSG group had increased levels of lipid hydroperoxide and decreased levels of total antioxidant substances. Levels of triacylglycerol and lipid hydroperoxide were decreased in rats fed the fiber-enriched and fiber- and MSG-enriched diets, whereas levels of total antioxidant substances were increased in these animals. Conclusions: MSG added to a standard diet increased food intake. Overfeeding induced metabolic disorders associated with oxidative stress in the absence of obesity. The fiber-enriched diet prevented changes in glucose, insulin, leptin, and triacylglycerol levels that were seen in the MSG group. Because the deleterious effects of MSG, i.e., induced overfeeding, were not seen in the animals fed the fiber-enriched diets, it can be concluded that fiber supplementation is beneficial by discouraging overfeeding and improving oxidative stress that is induced by an MSG diet. © 2005 Elsevier Inc. All rights reserved.

The β-chemokines MIP-1α and RANTES and lipoprotein metabolism in HIV-infected Brazilian patients

HIV patients are predisposed to the development of hypertriglyceridemia and hypercholesterolemia as a result of both viral infection and HIV infection therapy, especially the protease inhibitors. Chemokines and cytokines are present at sites of inflammation and can influence the nature of the inflammatory response in atherosclerosis. We investigated the correlation between biochemical variables and β-chemokines (MIP-1α and RANTES) and the apolipoprotein E genotype in HIV-infected individuals. The apolipoproteins were measured by nephelometry. Triglycerides and total cholesterol were determined by standard enzymatic procedures. The β-chemokines were detected by ELISA. The genetic category of CCR5 and apolipoprotein E were determined by PCR amplification and restriction enzymes. Immunological and virological profiles were assessed by TCD4 + and TCD8 + lymphocyte counts and viral load quantification. Positive correlations were found between apo E and CD8 + (p = 0.035), apo E and viral load (p = 0.018), MIP-1α and triglycerides (p = 0.039) and MIP-1α and VLDL (p = 0.040). Negative correlations were found between viral load and CD4 + (p = 0.05) and RANTES and CD4 + (p = 0.029). The β-chemokine levels may influence lipid metabolism in HIV-infected individuals. © 2005 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved.

High cholesterol intake modifies chylomicron metabolism in normolipidemic young men

Whether the consumption of egg yolk, which has a very high cholesterol content without excess saturated fats, has deleterious effects on lipid metabolism is controversial. Absorbed dietary cholesterol enters the bloodstream as chylomicrons, but the effects of regular consumption of large amounts of cholesterol on the metabolism of this lipoprotein have not been explored even though the accumulation of chylomicron remnants is associated with coronary artery disease (CAD). We investigated the effects of high dietary cholesterol on chylomicron metabolism in normolipidemic, healthy young men. The plasma kinetics of a chylomicron-like emulsion, doubly-labeled with 14C-cholesteryl ester ( 14C-CE) and 3H-triolein ( 3H-TG) were assessed in 25 men (17-22 y old, BMI 24.1 ± 3.4 kg/m 2). One group (n = 13) consumed 174 ± 41 mg cholesterol/d and no egg yolk. The other group (n = 12) consumed 3 whole eggs/d for a total cholesterol intake of 804 ± 40 mg/d. The nutritional composition of diets was the same for both groups, including total lipids and saturated fat, which comprised 25 and 7%, respectively, of energy intake. Serum LDL and HDL cholesterol and apoprotein B concentrations were higher in the group consuming the high-cholesterol diet (P < 0.05), but serum triacylglycerol, apo AI, and lipoprotein (a) did not differ between the 2 groups. The fractional clearance rate (FCR) of the 14C-CE emulsion, obtained by compartmental analysis, was 52% slower in the high-cholesterol than in the low-cholesterol group (P < 0.001); the 3H-TG FCR did not differ between the groups. Finally, we concluded that high cholesterol intakes increase the residence time of chylomicron remnants, as indicated by the 14C-CE kinetics, which may have undesirable effects related to the development of CAD. © 2006 American Society for Nutrition.

Importancia del diagnóstico precoz de los lipomas de células grandes en la región maxilofacial

Lipoma is a benign tumor composed of proliferation of mature fat cells interspersed by fibrous connective tissue, blood vessels and muscles, delimited by a thin capsule. Although it represents a mesenchymal neoplasm most common human body, are rare occurrences in the oral cavity. Presents clinical and histopathological variables that do not alter their prognosis. The pathogenesis is still uncertain, although some authors consider heredity and endocrine disorders as possible causes. Occurs with greater prevalence in obese people, although their metabolism is completely independent of the normal body lipid metabolism. The clinical diagnosis of oral lipoma is the view of a nodular mass, soft, asymptomatic, flat surface, without ulceration and limited growth. The continuing growth of the lesion may cause difficulty in chewing, speech, dental adaptation and change in facial aesthetics of the patient, requiring surgical excision of the lesion. The final diagnosis is by histopathological examination. Aims to present a literature review and clinical cases of a retrospective study of 61 cases of lipomas diagnosed in pathological service between 1978 and 2009, among the 10 573 reports during that same period. It emphasizes the special cases of large lipomas of the maxillofacial region, and the importance of early diagnosis of these lesions. A dental surgeon should be able to diagnose lipomas in an early stage in the maxillofacial area avoiding a massive growth of these lesions.