Using transient elastography to detect chronic liver diseases in a primary care nurse consultancy

Background: Chronic liver diseases (CLDs) are significant causes of death in adults in many countries and are usually diagnosed at late stages. Early detection may allow time for treatment to prevent disease progression. Objectives: The aim of this study was to assess the feasibility of screening for unrecognized CLDs in a primary care nurse consultancy and report findings from screening. Methods: Two experienced nurses in a primary care nurse consultancy were trained to perform transient elastography (TE). Subjects aged from 18 to 70 years were identified randomly from the health registry and invited to participate in a feasibility pilot study. Exclusion criteria were past or current history of liver diseases. Nurses collected demographic and clinical data and performed TE tests using Fibroscan tomeasure liver stiffness; a cutoff score of 6.8 kPa or greater was used as an indicator of the presence of CLD with fibrosis. Results: Accurate measurements were obtained in 495 of 502 participants (98.6%). Prevalence of elevated liver stiffness was observed in 28 of 495 subjects (5.7%). Compared to patients with normal liver stiffness, patients with increased liver stiffness were older, were more frequently male, and had higher frequency of metabolic syndrome. Nonalcoholic fatty liver was the most common cause of CLD. Discussion: Following training in procedures for conducting TE, nurses in a primary care clinic were able to detect unrecognized CLDs in presumably healthy subjects. Early detection of CLDs is feasible in primary care clinics and may facilitate identification of undiagnosed CLD in adults.

Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus

Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.

Simple sugar intake and hepatocellular carcinoma: epidemiological and mechanistic insight

Sugar intake has dramatically increased during the last few decades. Specifically, there has been a clear trend towards higher consumption of fructose and high fructose corn syrup, which are the most common added sugars in processed food, soft drinks and other sweetened beverages. Although still controversial, this rising trend in simple sugar consumption has been positively associated with weight gain and obesity, insulin resistance and type 2 diabetes mellitus and non-alcoholic fatty liver disease. Interestingly, all of these metabolic alterations have also been related to the development of hepatocellular carcinoma. The purpose of this review is to discuss the evidence coming from epidemiological studies and data from animal models relating the consumption of simple sugars, and specifically fructose, with an increased risk of hepatocellular carcinoma and to gain insight into the putative molecular mechanisms involved.

Sinusoidal Endothelial Dysfunction Precedes Inflammation and Fibrosis in a Model of NAFLD

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Most morbidity associated with the metabolic syndrome is related to vascular complications, in which endothelial dysfunction is a major pathogenic factor. However, whether NAFLD is associated with endothelial dysfunction within the hepatic vasculature is unknown. The aims of this study were to explore, in a model of diet-induced overweight that expresses most features of the metabolic syndrome, whether early NAFLD is associated with liver endothelial dysfunction. Wistar Kyoto rats were fed a cafeteria diet (CafD; 65% of fat, mostly saturated) or a control diet (CD) for 1 month. CafD rats developed features of the metabolic syndrome (overweight, arterial hypertension, hypertryglyceridemia, hyperglucemia and insulin resistance) and liver steatosis without inflammation or fibrosis. CafD rats had a significantly higher in vivo hepatic vascular resistance than CD. In liver perfusion livers from CafD rats had an increased portal perfusion pressure and decreased endothelium-dependent vasodilation. This was associated with a decreased Akt-dependent eNOS phosphorylation and NOS activity. In summary, we demonstrate in a rat model of the metabolic syndrome that shows features of NAFLD, that liver endothelial dysfunction occurs before the development of fibrosis or inflammation.

Use of palm-oil by-products in chicken and rabbit feeds: effect on the fatty acid and tocol composition of meat, liver and plasma

This study was undertaken in the framework of a larger European project dealing with the characterization of fat co- and by-products from the food chain, available for feed uses. In this study, we compare the effects, on the fatty acid (FA) and tocol composition of chicken and rabbit tissues, of the addition to feeds of a palm fatty acid distillate, very low in trans fatty acids (TFA), and two levels of the corresponding hydrogenated by-product, containing intermediate and high levels of TFA. Thus, the experimental design included three treatments, formulated for each species, containing the three levels of TFA defined above. Obviously, due to the use of hydrogenated fats, the levels of saturated fatty acids (SFA) show clear differences between the three dietary treatments. The results show that diets high in TFA (76 g/kg fat) compared with those low in TFA (4.4 g/kg fat) led to a lower content of tocopherols and tocotrienols in tissues, although these differences were not always statistically significant, and show a different pattern for rabbit and chicken. The TFA content in meat, liver and plasma increased from low-to-high TFA feeds in both chicken and rabbit. However, the transfer ratios from feed were not proportional to the TFA levels in feeds, reflecting certain differences according to the animal species. Moreover, feeds containing fats higher in TFA induced significant changes in tissue SFA, monounsaturated fatty acids and polyunsaturated fatty acids composition, but different patterns can be described for chicken and rabbit and for each type of tissue.

Use of recovered frying oils in chicken and rabbit feeds: effect on the fatty acid and tocol composition and on the oxidation levels of meat, liver and plasma

The addition of some fat co- and by-products to feeds is usual nowadays; however, the regulations of their use are not always clear and vary between countries. For instance, the use of recycled cooking oils is not allowed in the European Union, but they are used in other countries. However, oils recovered from industrial frying processes could show satisfactory quality for this purpose. Here we studied the effects of including oils recovered from the frying industry in rabbit and chicken feeds (at 30 and 60 g/kg, respectively) on the fatty acid (FA) and tocol (tocopherol + tocotrienol) compositon of meat, liver and plasma, and on their oxidative stability. Three dietary treatments (replicated eight times) were compared: fresh non-used oil (LOX); oil discarded from the frying industry, having a high content of secondary oxidation compounds (HOX); and an intermediate level (MOX) obtained by mixing 50 : 50 of LOX and HOX. The FA composition of oil diets and tissues was assessed by GC, their tocol content by HPLC, the thiobarbituric acid value was used to assess tissue oxidation status, and the ferrous oxidation-xylenol orange method was used to assess the susceptibility of tissues to oxidation. Our results indicate that FA composition of rabbit and chicken meat, liver and plasma was scarcely altered by the addition of recovered frying oils to feed. Differences were encountered in the FA composition between species, which might be attributed mainly to differences in the FA digestion, absorption and metabolism between species, and to some physiological dietary factors (i.e. coprophagy in rabbits that involves fermentation with FA structure modification). The α-tocopherol (αT) content of tissues was reduced in response to the lower αT content in the recovered frying oil. Differences in the content of other tocols were encountered between chickens and rabbits, which might be attributable to the different tocol composition of their feeds, as well as to species differences in the digestion and metabolism of tocols. Tissue oxidation and susceptibility to oxidation were in general low and were not greatly affected by the degree of oxidation of the oil added to the feeds. The relative content of polyunsaturated fatty acids/αT in these types of samples would explain the differences observed between species in the susceptibility of each tissue to oxidation. According to our results, oils recovered from the frying industry could be useful for feed uses.

Fructose induces synthesis and reduces oxidation of liver fatty acids through ChREBP activation

Introduction and aims. During last few decades, the prevalence of obesity, metabolic syndrome and insulin resistance, among other metabolic disturbances, has raised considerably in many countries worldwide. Environmental factors (diet, physical activity), in tandem with predisposing genetic factors, may be responsible for this trend. Along with an increase in total energy consumption during recent decades, there has also been a shift in the type of nutrients, with an increased consumption of fructose, largely attributable to a greater intake of beverages containing high levels of fructose...

Fructose induces synthesis and reduces oxidation of liver fatty acids through ChREBP activation

Introduction and aims. During last few decades, the prevalence of obesity, metabolic syndrome and insulin resistance, among other metabolic disturbances, has raised considerably in many countries worldwide. Environmental factors (diet, physical activity), in tandem with predisposing genetic factors, may be responsible for this trend. Along with an increase in total energy consumption during recent decades, there has also been a shift in the type of nutrients, with an increased consumption of fructose, largely attributable to a greater intake of beverages containing high levels of fructose...

Use of recovered frying oils in chicken and rabbit feeds: effect on the fatty acid and tocol composition and on the oxidation levels of meat, liver and plasma

The addition of some fat co- and by-products to feeds is usual nowadays; however, the regulations of their use are not always clear and vary between countries. For instance, the use of recycled cooking oils is not allowed in the European Union, but they are used in other countries. However, oils recovered from industrial frying processes could show satisfactory quality for this purpose. Here we studied the effects of including oils recovered from the frying industry in rabbit and chicken feeds (at 30 and 60 g/kg, respectively) on the fatty acid (FA) and tocol (tocopherol + tocotrienol) compositon of meat, liver and plasma, and on their oxidative stability. Three dietary treatments (replicated eight times) were compared: fresh non-used oil (LOX); oil discarded from the frying industry, having a high content of secondary oxidation compounds (HOX); and an intermediate level (MOX) obtained by mixing 50 : 50 of LOX and HOX. The FA composition of oil diets and tissues was assessed by GC, their tocol content by HPLC, the thiobarbituric acid value was used to assess tissue oxidation status, and the ferrous oxidation-xylenol orange method was used to assess the susceptibility of tissues to oxidation. Our results indicate that FA composition of rabbit and chicken meat, liver and plasma was scarcely altered by the addition of recovered frying oils to feed. Differences were encountered in the FA composition between species, which might be attributed mainly to differences in the FA digestion, absorption and metabolism between species, and to some physiological dietary factors (i.e. coprophagy in rabbits that involves fermentation with FA structure modification). The α-tocopherol (αT) content of tissues was reduced in response to the lower αT content in the recovered frying oil. Differences in the content of other tocols were encountered between chickens and rabbits, which might be attributable to the different tocol composition of their feeds, as well as to species differences in the digestion and metabolism of tocols. Tissue oxidation and susceptibility to oxidation were in general low and were not greatly affected by the degree of oxidation of the oil added to the feeds. The relative content of polyunsaturated fatty acids/αT in these types of samples would explain the differences observed between species in the susceptibility of each tissue to oxidation. According to our results, oils recovered from the frying industry could be useful for feed uses.

Dietary n-6- or n-3-rich vegetable fats and antioxidants: effects on fatty acid composition and stability of rabbit plasma, liver and meat

We supplemented diets with a-tocopheryl acetate (100 mg/kg) and replaced beef tallow (BT) in feeds with increasing doses of n-6- or n-3-rich vegetable fat sources (linseed and sunflower oil), and studied the effects on the fatty acid (FA) composition, the a-tocopherol (aT) content and the oxidative stability of rabbit plasma and liver. These effects were compared with those observed in a previous study in rabbit meat. As in meat, the content of saturated, monounsaturated and trans FA in plasma and liver mainly reflected feed FA profile, except stearic acid in liver, which increased as feeds contained higher doses of vegetable fat, which could be related to an inhibition of the activity of the stearoyl-CoA-desaturase. As linseed oil increased in feeds, the n-6/n-3 FA ratio was decreased in plasma and liver as a result of the incorporation of FA from diets and also, due to the different performance and selectivity of desaturase enzymes. However, an increase in the dose of vegetable fat in feeds led to a significant reduction in the aT content of plasma and liver, which was greater when the fat source was linseed oil. Increasing the dose of vegetable fat in feeds also led to an increase in the susceptibility to oxidation (lipid hydroperoxide (LHP) value) of rabbit plasma, liver and meat and on the thiobarbituric acid (TBA) values of meat. Although the dietary supplementation with a-tocopheryl acetate increased the aT content in plasma and liver, it did not modify significantly their TBA or LHP values. In meat however, both TBA and LHP values were reduced by the dietary supplementation with a-tocopheryl acetate. The plasma aT content reflected the aT content in tissues, and correlated negatively with tissue oxidability. From the studied diets, those containing 1.5% linseed oil plus 1.5% BT and 100 mg of a-tocopheryl acetate/kg most improved the FA composition and the oxidative stability of rabbit tissues.

Use of recovered frying oils in chicken and rabbit feeds: effect on the fatty acid and tocol composition and on the oxidation levels of meat, liver and plasma

The addition of some fat co- and by-products to feeds is usual nowadays; however, the regulations of their use are not always clear and vary between countries. For instance, the use of recycled cooking oils is not allowed in the European Union, but they are used in other countries. However, oils recovered from industrial frying processes could show satisfactory quality for this purpose. Here we studied the effects of including oils recovered from the frying industry in rabbit and chicken feeds (at 30 and 60 g/kg, respectively) on the fatty acid (FA) and tocol (tocopherol1tocotrienol) compositon of meat, liver and plasma, and on their oxidative stability. Three dietary treatments (replicated eight times) were compared: fresh non-used oil (LOX); oil discarded from the frying industry, having a high content of secondary oxidation compounds (HOX); and an intermediate level (MOX) obtained by mixing 50 : 50 of LOX and HOX. The FA composition of oil diets and tissues was assessed by GC, their tocol content by HPLC, the thiobarbituric acid value was used to assess tissue oxidation status, and the ferrous oxidation-xylenol orange method was used to assess the susceptibility of tissues to oxidation. Our results indicate that FA composition of rabbit and chicken meat, liver and plasma was scarcely altered by the addition of recovered frying oils to feed. Differences were encountered in the FA composition between species, which might be attributed mainly to differences in the FA digestion, absorption and metabolism between species, and to some physiological dietary factors (i.e. coprophagy in rabbits that involves fermentation with FA structure modification). The a-tocopherol (aT) content of tissues was reduced in response to the lower aT content in the recovered frying oil. Differences in the content of other tocols were encountered between chickens and rabbits, which might be attributable to the different tocol composition of their feeds, as well as to species differences in the digestion and metabolism of tocols. Tissue oxidation and susceptibility to oxidation were in general low and were not greatly affected by the degree of oxidation of the oil added to the feeds. The relative content of polyunsaturated fatty acids/aT in these types of samples would explain the differences observed between species in the susceptibility of each tissue to oxidation. According to our results, oils recovered from the frying industry could be useful for feed uses.

Oxidized oils and dietary zinc and alpha-tocopheryl acetate supplementation: effects on rabbit plasma, liver and meat fatty acid composition and meat Zn, Cu, Fe and Se content

The effects of the addition of heated oils to feeds (3%, w/w) and the dietary supplementation with a-tocopheryl acetate (TA; 100 mg/kg) and Zn (200 mg/kg) on rabbit tissue fatty acid (FA) composition and on the Zn, Cu, Fe and Se content in meat were assessed. Heating unrefined sunflower oil (SO) at 558C for 245 h increased its content in primary oxidation products and reduced its a-tocopherol content. However, this did not significantly affect tissue FA composition. Heating SO at 1408C for 31 h increased its content in secondary oxidation products and in some FA isomers asc9,t11-CLA and di-trans CLA. This led to increases in di-trans CLA in liver and in t9,c12-18:2 in meat. The c9,t11-CLA was the most incorporated CLA isomer in tissues. The dietary supplementation with a-TA did not affect the FA composition of plasma, liver or meat. The cooking of vacuum-packed rabbit meat at 788C for 5 min reduced significantly but slightly its polyunsaturated FA content. The dietary supplementation with Zn did not modify the content of Zn, Fe or Se in meat, but it reduced its Cu content. On the other hand, it increased the content of some FAs in meat when SO heated at 1408C for 31 h was added to feeds.

Mitochondrial Fatty Acid Oxidation in Obesity

Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders. Antioxid. Redox Signal. 00, 000000.

Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate

FSP27 (CIDEC in humans) is a protein associated with lipid droplets that downregulates the fatty acid oxidation (FAO) rate when it is overexpressed. However, little is known about its physiological role in liver. Here, we show that fasting regulates liver expression of Fsp27 in a time-dependent manner. Thus, during the initial stages of fasting a maximal induction of 800-fold was achieved, while during the later phase of fasting, Fsp27 expression decreased. The early response to fasting can be explained by a canonical PKA-CREB-CRTC2 signaling pathway since: i) CIDEC expression was induced by forskolin, ii) Fsp27 promoter activity was increased by CREB, and iii) Fsp27 expression was upregulated in the liver of Sirt1 knockout animals. Interestingly, pharmacological (etomoxir) or genetic (Hmgcs2 interference) inhibition of the FAO rate increases the in vivo expression of Fsp27 during fasting. Similarly, CIDEC expression was upregulated in HepG2 cells by either etomoxir or HMGCS2 interference. Our data indicate that there is a kinetic mechanism of auto-regulation between short- and long-term fasting, by which free fatty acids delivered to the liver during early fasting are accumulated/exported by FSP27/CIDEC, while over longer periods of fasting they are degraded in the mitochondria through the carnitine palmitoyl transferase (CPT) system.

New strategies in the modulation of fatty acid oxidation as a treatment for obesity

Strategies that enhance fat degradation or reduce caloricfood intake could be considered therapeutic interventions to reduce notonly obesity, but also its associated disorders. The enzyme carnitinepalmitoyltransferase 1 (CPT1) is the critical rate-determining regulatorof fatty acid oxidation (FAO) and might play a key role in increasingenergy expenditure and controlling food intake. Our group has shownthat mice overexpressing CPT1 in liver are protected from weight gain,the development of obesity and insulin resistance. Regarding foodintake control, we observed that the pharmacological inhibition ofCPT1 in rat hypothalamus decreased food intake and body weight.This suggests that modulation of CPT1 activity and the oxidation offatty acids in various tissues can be crucial for the potential treatmentof obesity and associated pathologies.