Changes in brown adipose tissue induced by resveratrol and its analogue pterostilbene in rats fed with a high-fat high-fructose diet.

Natural bioactive compounds have attracted a great deal of attention since some of them can act as thermogenesis activators. In recent years, special interest has been placed on resveratrol and its analogue pterostilbene, a dimethylether derivative that shows higher bioavailability. The aim of the present study is to compare the effects of resveratrol and its derivative pterostilbene on the thermogenic capacity of interscapular brown adipose tissue (iBAT) in rats under a high-fat high-fructose diet. Rats were divided into four experimental groups: control, high-fat high-fructose diet (HFHF) and HFHF diet supplemented with 30 mg/kg body weight/day of pterostilbene (PT30) or resveratrol (RSV30), for eight weeks. Weights of adipose tissues, iBAT triglycerides, carnitine palmitoyltransferase 1A (CPT1A) and citrate synthase (CS) activities, protein levels of uncoupling protein 1 (UCP1), sirtuins (SIRT1 and 3), AMP-activated protein kinase (AMPK), glucose transporter (GLUT4), fatty acid synthase (FAS), nuclear respiratory factor (NRF1), hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), CD36 and FATP1 fatty acid transporters, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) activation and the batokines EPDR1 and NRG4 were assessed in iBAT. The results show that some key proteins related to thermogenesis were modified by either pterostilbene or resveratrol, although the lack of effects on other crucial proteins of the thermogenic machinery suggest that these compounds were not able to stimulate this process in iBAT. Overall, these data suggest that the effects of stilbenes on brown adipose tissue thermogenic capacity depend on the metabolic status, and more precisely on the presence or absence of obesity, although further studies are needed to confirm this hypothesis.

Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis.

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient´s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients.

Scientific Evidence Supporting the Beneficial Effects of Isoflavones on Human Health.

Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level.

Activity of Pterostilbene Metabolites against Liver Steatosis in Cultured Hepatocytes.

Pterostilbene is a dimethyl ether derivative of resveratrol, less metabolized than its analogue, due to the substitution of two hydroxyl groups with methoxyl groups. Nevertheless, the amounts of pterostilbene phase II metabolites found in plasma and tissues are higher than those of the parent compound. The first aim of this study was to assess whether pterostilbene-4'-O-glucuronide (PT-G) and pterostilbene-4'-O-sulfate (PT-S) were able to prevent triglyceride accumulation in AML12 (alpha mouse liver 12) hepatocytes. This being the case, we aimed to analyze the mechanisms involved in their effects. For this purpose, an in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10 or 25 µM of pterostilbene, pterostilbene-4'-O-glucuronide or pterostilbene-4'-O-sulfate for 18 h. Triglycerides and cell viability were assessed by a commercial kit and crystal violet assay, respectively. Protein expression of enzymes and transporters involved in triglyceride metabolism was analyzed by immunoblot. The results showed for the first time the anti-steatotic effect of pterostilbene metabolites and thus, that they contribute to the preventive effect induced by pterostilbene on steatosis in in vivo models. This anti-steatotic effect is mainly due to the inhibition of de novo lipogenesis.

Comparative Effects of Pterostilbene and Its Parent Compound Resveratrol on Oxidative Stress and Inflammation in Steatohepatitis Induced by High-Fat High-Fructose Feeding.

Different studies have revealed that oxidative stress and inflammation are crucial in NAFLD (Non-alcoholic fatty liver disease). The aim of this study is to analyze whether pterostilbene and resveratrol are able to either avoid or delay the progression of non-alcoholic liver steatosis towards steatohepatitis. This has been performed by examining their effects on oxidative stress, inflammation, fibrosis and pre-carcinogenic stages. Rats were distributed into five experimental groups and were fed with either a standard diet or a high-fat high-fructose diet, supplemented or not with pterostilbene (15 or 30 mg/kg/d) or resveratrol (30 mg/kg/d), for 8 weeks. Liver histological analysis was carried out by haematoxylin-eosin staining. Serum and hepatic oxidative stress-related parameters were assessed using spectrophotometry, and the expression of genes related to inflammation, fibrosis and cancer by qRT-PCR. The dietary model used in this study led to the development of steatohepatitis, where rats displayed oxidative stress, inflammation and ballooning, although not fibrosis. It also modified the expression of hepatocarcinoma-related genes. The results show, for the first time, that pterostilbene was able to partially prevent these alterations, with the exception of changes in hepatocarcinoma-related genes, mainly at 30 mg/kg/d. Pterostilbene was more effective than its parent compound resveratrol, probably due to its high bioavailability and higher anti-oxidant and anti-inflammatory activities, attributable to its different chemical structure.

Resveratrol Metabolites Are Able to Reduce Steatosis in Cultured Hepatocytes.

Steatosis is characterized primarily by excessive lipid accumulation in the form of triglycerides in the liver. Although resveratrol shows a low bioavailability, it has significant positive effects on steatosis. The aim of this study was to analyze whether some phase II and microbial resveratrol metabolites (trans-resveratrol-4'-O-glucuronide (R-4G); trans-resveratrol-3-O-glucuronide (R-3G); trans-resveratrol-3-O-sulfate (R-S) and dihydro-resveratrol (DH-R) were effective in reducing hepatocyte fat accumulation. An in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10, or 25 µM resveratrol or its metabolites. Triglycerides and cell viability were assessed using commercial kits. Protein expression of enzymes and transporters involved in triglyceride metabolism were analyzed by western blot. We show for the first time that resveratrol and all the tested metabolites, at 1 µM, partially prevented lipid accumulation induced by the saturated fatty acid PA in AML12 hepatocytes. This effect was mainly due to the inhibition of de novo lipogenesis. This demonstrates that the low bioavailability of resveratrol is not as big a problem as it was thought to be, because resveratrol metabolites contribute to the delipidating effects of the parent compound.

Association of lifestyle factors and inflammation with sarcopenic obesity: data from the PREDIMED-Plus trial.

BACKGROUND: Sarcopenia is a progressive age-related skeletal muscle disorder associated with increased likelihood of adverse outcomes. Muscle wasting is often accompanied by an increase in body fat, leading to 'sarcopenic obesity'. The aim of the present study was to analyse the association of lifestyle variables such as diet, dietary components, physical activity (PA), body composition, and inflammatory markers, with the risk of sarcopenic obesity. METHODS: A cross-sectional analysis based on baseline data from the PREDIMED-Plus study was performed. A total of 1535 participants (48% women) with overweight/obesity (body mass index: 32.5 ± 3.3 kg/m2 ; age: 65.2 ± 4.9 years old) and metabolic syndrome were categorized according to sex-specific tertiles (T) of the sarcopenic index (SI) as assessed by dual-energy X-ray absorptiometry scanning. Anthropometrical measurements, biochemical markers, dietary intake, and PA information were collected. Linear regression analyses were carried out to evaluate the association between variables. RESULTS: Subjects in the first SI tertile were older, less physically active, showed higher frequency of abdominal obesity and diabetes, and consumed higher saturated fat and less vitamin C than subjects from the other two tertiles (all P < 0.05). Multiple adjusted linear regression models evidenced significant positive associations across tertiles of SI with adherence to the Mediterranean dietary score (P-trend < 0.05), PA (P-trend < 0.0001), and the 30 s chair stand test (P-trend < 0.0001), whereas significant negative associations were found with an inadequate vitamin C consumption (P-trend < 0.05), visceral fat and leucocyte count (all P-trend < 0.0001), and some white cell subtypes (neutrophils and monocytes), neutrophil-to-lymphocyte ratio, and platelet count (all P-trend < 0.05). When models were additionally adjusted by potential mediators (inflammatory markers, diabetes, and waist circumference), no relevant changes were observed, only dietary variables lost significance. CONCLUSIONS: Diet and PA are important regulatory mediators of systemic inflammation, which is directly involved in the sarcopenic process. A healthy dietary pattern combined with exercise is a promising strategy to limit age-related sarcopenia.

Preparation and Characterization of Resveratrol Loaded Pectin/Alginate Blend Gastro-Resistant Microparticles.

BACKGROUND: The use of resveratrol as a dietary supplement is limited because it is easily oxidized and, after oral ingestion, it is metabolized into enterocytes and hepatocytes. Thus, new formulations are needed in order to improve its oral bioavailability. OBJECTIVE: The objective of this study was to develop and characterize a gastro-resistant formulation of resveratrol for oral administration as a dietary supplement. METHOD: Resveratrol was encapsulated in Eudragit-coated pectin-alginate microparticles. RESULTS: The microparticle size was about 1450 µm, with an encapsulation efficiency of 41.72% ± 1.92%. The dissolution assay conducted, as specified in the European Pharmacopoeia for delayed-release dosage forms, revealed that our microparticles were gastro-resistant, because the resveratrol percentage released from microparticles in acid medium was less than 10%. In addition, the high-performance liquid chromatographic (HPLC) method developed for resveratrol content quantification in the microparticles was validated according to International Council for Harmonisation (ICH) Q2 (R1) guidelines. Finally, the biological activity of resveratrol was investigated in 3T3-L1 mature adipocytes, concluding that the encapsulation process does not affect the activity of resveratrol. CONCLUSION: In summary, the gastro-resistant microparticles developed could represent a suitable method of including resveratrol in dietary supplements and in functional foods used in obesity therapy.

Polyphenol Levels Are Inversely Correlated with Body Weight and Obesity in an Elderly Population after 5 Years of Follow Up (The Randomised PREDIMED Study).

Overweight and obesity have been steadily increasing in recent years and currently represent a serious threat to public health. Few human studies have investigated the relationship between polyphenol intake and body weight. Our aim was to assess the relationship between urinary polyphenol levels and body weight. A cross-sectional study was performed with 573 participants from the PREDIMED (Prevención con Dieta Mediterránea) trial (ISRCTN35739639). Total polyphenol levels were measured by a reliable biomarker, total urinary polyphenol excretion (TPE), determined by the Folin-Ciocalteu method in urine samples. Participants were categorized into five groups according to their TPE at the fifth year. Multiple linear regression models were used to assess the relationships between TPE and obesity parameters; body weight (BW), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR). After a five years follow up, significant inverse correlations were observed between TPE at the 5th year and BW (ß = -1.004; 95% CI: -1.634 to -0.375, p = 0.002), BMI (ß = -0.320; 95% CI: -0.541 to -0.098, p = 0.005), WC (ß = -0.742; 95% CI: -1.326 to -0.158, p = 0.013), and WHtR (ß = -0.408; 95% CI: -0.788 to -0.028, p = 0.036) after adjustments for potential confounders. To conclude, a greater polyphenol intake may thus contribute to reducing body weight in elderly people at high cardiovascular risk.

Effects of resveratrol and other polyphenols in hepatic steatosis.

Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic steatohepatitis. Polyphenols are members of a very large family of plant-derived compounds that can have beneficial effects on human health, and thus their study has become an increasingly important area of human nutrition research. The aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts, on hepatocyte and liver fat accumulation under different steatosis-inducing conditions. The results reported clearly show that this group of biomolecules is able to reduce fat accumulation, but further studies are needed to establish the optimal dose and treatment period length. With regard to the potential mechanisms of action, there is a good consensus. The anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis, increased in fatty acid oxidation, and reduced of oxidative stress and inflammation. As a general conclusion, it can be stated that polyphenols are biomolecules which produce hepatoprotective effects. To date, these beneficial effects have been demonstrated in cultured cells and animal models. Thus, studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis.

Lifestyles and risk factors associated with adherence to the Mediterranean diet: a baseline assessment of the PREDIMED trial.

BACKGROUND: The traditional Mediterranean dietary pattern (MedDiet) is associated with longevity and low rates of cardiovascular disease (CVD). However, there is little information on who is more likely to follow this food pattern. AIM: To evaluate how different factors are associated with lower MedDiet adherence in older Spanish subjects. METHODS: We included 7305 participants (men aged 55-80 y, women 60-80 y) at high-risk of CVD recruited into the PREDIMED trial (ISRCTN35739639). Socioeconomic, anthropometric, lifestyle characteristics and CVD risk factors were recorded. A validated 14-item questionnaire was used to evaluate MedDiet adherence at baseline. Multivariate models were used to estimate odds ratios (OR) and 95% confidence intervals for lower adherence to the MedDiet (<9 points out of 14) and ascertain factors independently associated with it. RESULTS: Former smoking (OR = 0.87; 95% CI, 0.78-0.98), physical activity (OR for the 3(rd) vs. the 1(st)tertile: 0.69; 0.62-0.78), and higher educational level (OR for university vs. less than primary school: 0.54; 0.38-0.77) were associated with higher MedDiet adherence. Conversely, having a larger waist-to-height ratio (OR for 0.1 units, 1.35; 1.22-1.49), being diabetic (OR = 1.13; 1.03-1.24), being single (OR = 1.27; 1.01-1.61) or divorced or separated (OR = 1.44; 1.09-1.89), and current smoking (OR = 1.28; 1.11-1.47) were associated with lower adherence. CONCLUSIONS: Participants with little education, a larger waist-to-height ratio, or diabetes and those who were less physically active, single, divorced or separated, or smokers were less likely to adhere to the MedDiet, an ideal model for food choices. Stronger efforts of health promotion are needed in these groups to foster adoption of the MedDiet.

The combination of resveratrol and conjugated linoleic acid is not useful in preventing obesity.

Scientific research is constantly looking for new molecules to be used as functional ingredients to combat obesity. The aim of the present study was to analyse whether resveratrol and conjugated linoleic acid (CLA) together could reduce body fat more efficiently than their separate administration. Thirty-six male Wistar rats were randomly divided into four groups: controls rats (C), rats treated with resveratrol (RSV), rats treated with CLA (CLA) and rats treated with a combination of resveratrol and CLA (RSV+CLA). All rats were fed on an obesogenic diet. In RSV and RSV+CLA groups, the rats received 30 mg resveratrol/kg body weight/day. In CLA and RSV+CLA groups, an equimolecular mixture of trans-10,cis-12 and cis-9,trans-11 was added to the diet to reach 0.5% of the active isomer trans-10,cis-12. After 6 weeks of treatment, white adipose tissue from different anatomical locations was dissected and weighed. Serum triacylglycerols, total and HDL cholesterols, glucose, insulin, fructosamine and TNF-α were measured. A glucose tolerance test was also performed. Separately, resveratrol and CLA significantly reduced body fat but did not do so when combined: 20% in the RSV group and 18% in CLA group but 7% in the RSV+CLA group. Resveratrol reduced serum triacylglycerols. No differences were found among groups in serum cholesterol. Resveratrol, as well as the combination RSV+CLA, improved glycaemic control. These results demonstrate that the combination RSV+CLA reduces the effectiveness of each compound on body fat-lowering action, but it maintains the positive effect of resveratrol on glycaemic control. Consequently, this combination has no usefulness in obesity prevention.

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats.

Thrombospondin 1 (TSP-1), an antiangiogenic factor and transforming growth factor (TGF)-ß activity regulator, has been recently recognized as an adipokine that correlates with obesity, inflammation and insulin resistance processes. In the present study, epididymal adipocytes of rats that were fed a chow or a high-fat diet (HFD) for 50 days were isolated and incubated (24-72 h) in low (5.6 mM) or high (HG; 25 mM) glucose, in the presence or absence of 1.6 nM insulin. Rats fed the HF diet showed an established obesity state. Serum TSP-1 levels and TSP-1 mRNA basal expression of adipocytes from HFD rats were higher than those from controls. Adipocytes from HFD animals presented an insulin resistance state, as suggested by the lower insulin-stimulated glucose uptake as compared to controls. TSP-1 expression in culture was higher in adipocytes from obese animals at 24 h, but when the adipocytes were treated with HG, these expression levels dropped dramatically. Later at 72 h, TSP-1 expression was lower in adipocytes from HFD rats, and no effects of the other treatments were observed. Surprisingly, the secretion levels of this protein at 72 h were increased significantly by the HG treatment in both types of adipocytes, although they were even higher in adipocytes from obese animals. Finally, cell viability was significantly reduced by HG treatment in both types of adipocytes. In summary, TSP-1 expression/secretion was modulated in an in vitro model of insulin-resistant adipocytes. The difference between expression and secretion patterns suggests a posttranscriptional regulation. The present study confirms that TPS-1 is closely associated with obesity-related mechanisms.

Effects of trans-10,cis-12 CLA on liver size and fatty acid oxidation under energy restriction conditions in hamsters.

OBJECTIVE: Little evidence exists concerning the effects of trans-10,cis-12 conjugated linoleic acid (CLA) under energy restriction. Thus, the effects of this CLA isomer on adipose tissue size, liver composition, as well as on expression and activity of carnitine-palmitoyl transferase I (CPT-I) and acyl CoA oxidase (ACO), in hamsters fed an energy-restricted diet were analyzed. METHODS: Hamsters were fed a high-fat diet for 7 wk and then subjected to 25% energy-restricted diets supplemented with 0.5% linoleic acid or 0.5% trans-10,cis-12 CLA for 3 wk. Serum insulin, free-triiodothyronine and non-esterified fatty acid levels, liver triacylglycerol, protein and water contents, and CPT-I, ACO, and Peroxisome proliferator-activated receptor alpha (PPARα) expressions and enzyme activities were assessed. RESULTS: Energy restriction reduced liver size, serum levels of insulin, free-triiodothyronine, and non-esterified fatty acid and increased CPT-I activity. Liver composition was not modified. No differences were found between both restricted groups, with the exception of CPT-I and ACO oxidative enzyme activities, which were greater in hamsters fed the CLA diet. CONCLUSIONS: Energy restriction does not cause trans-10,cis-12 CLA to induce liver hyperplasia. Although this CLA isomer increases liver CPT-I and ACO activities, this effect does not result in reduced hepatic triacylglyerol content or decreased adipose tissue size. Consequently, this CLA isomer seems not to be a useful tool for inclusion in body weight loss strategies followed during obesity treatment.

Weak effect of trans-10, cis-12-conjugated linoleic acid on body fat accumulation in adult hamsters.

It has been proposed that young animals and subjects are more responsive to conjugated linoleic acid (CLA) than the adults. Nevertheless, there is very little information concerning the effectiveness of CLA in adult animals. In the present study we aimed to explore the effects of trans-10, cis-12-CLA on body fat accumulation in adult hamsters, as well as on some of the molecular mechanisms described in young animals as responsible for the CLA body fat-lowering effect, such as lipogenesis, lipoprotein lipase (LPL)-mediated fat uptake and thermogenesis. The experiment was conducted with sixteen adult male Syrian Golden hamsters (aged 8 months) fed a high-fat diet supplemented or not with 0.5 % trans-10, cis-12-CLA for 6 weeks. Acetyl-CoA carboxylase (ACX), fatty acid synthase (FAS), LPL, PPARgamma, sterol regulatory element-binding protein (SREBP)-1a and SREBP-1c expressions were assessed in subcutaneous and perirenal adipose tissues by real-time RT-PCR. Total and heparin-releasable LPL activities were determined in subcutaneous adipose tissue by fluorimetry and FAS activity by spectrophotometry. Uncoupling protein-1 (UCP1) expression in interscapular brown adipose tissue was assessed by Western blot. Hamsters fed the trans-10, cis-12-CLA diet showed a significant reduction in subcutaneous adipose tissue. No changes were observed in the expression of ACX, FAS, LPL, SREBP-1a, SREBP-1c and PPARgamma, nor in total and heparin-releasable LPL and FAS activities. Trans-10, cis-12-CLA induced a significant increase in the amount of UCP1. These results suggest a low responsiveness to trans-10, cis-12-CLA in adults, lower than that in young hamsters. One of the reasons explaining this difference is the lack of effect on LPL.

Conjugated linoleic acid isomers: differences in metabolism and biological effects.

The term conjugated linoleic acid (CLA) refers to a mixture of linoleic acid positional and geometric isomers, characterized by having conjugated double bonds, not separated by a methylene group as in linoleic acid. CLA isomers appear as a minor component of the lipid fraction, found mainly in meat and dairy products from cows and sheep. The most abundant isomer is cis-9,trans-11, which represents up to 80% of total CLA in food. These isomers are metabolized in the body through different metabolic pathways, but important differences, that can have physiological consequences, are observed between the two main isomers. The trans-10,cis-12 isomer is more efficiently oxidized than the cis-9,trans-11 isomer, due to the position of its double bounds. Interest in CLA arose in its anticarcinogenic action but there is an increasing amount of specific scientific literature concerning the biological effects and properties of CLA. Numerous biological effects of CLA are due to the separate action of the most studied isomers, cis-9,trans-11 and trans-10,cis-12. It is also likely that some effects are induced and/or enhanced by these isomers acting synergistically. Although the cis-9,trans-11 isomer is mainly responsible for the anticarcinogenic effect, the trans-10,cis-12 isomer reduces body fat and it is referred as the most effective isomer affecting blood lipids. As far as insulin function is concerned, both isomers seem to be responsible for insulin resistance in humans. Finally, with regard to the immune system it is not clear whether individual isomers of CLA could act similarly or differently.

Effects of high-fat high-sucrose feeding, energy restriction, and trans-10,cis-12 conjugated linoleic acid on visfatin and apelin in hamsters.

OBJECTIVE: To analyze the effects of high-fat high-sucrose (HFHS) feeding, energy restriction, and trans-10,cis-12 conjugated linoleic acid (CLA) on visfatin and apelin. DESIGN: A randomized dietary intervention study. SETTING: Free-living individuals studied in metabolic cages. SUBJECTS: Thirty-two male Syrian Golden hamsters (82.6 +/- 1.4 g). INTERVENTIONS: Standard and HFHS feeding for 7 weeks. After that, some hamsters fed the HFHS diet were submitted for 3 weeks to a 25% energy restriction with or without trans-10,cis-12 CLA supplementation (0.5%). RESULTS: Feeding animals an HFHS diet resulted in increased body fat and reduced insulin sensitivity. No changes were observed in the expression and serum levels of visfatin and apelin, or in peroxisome proliferator-activated receptor (PPAR)gamma and Sirt1 expression. Energy restriction reduced body fat and normalized insulin sensitivity. Visfatin showed increased serum levels without changes in expression. No modifications were found as far as apelin was concerned. Sirt1 expression was increased, and PPARgamma remained unchanged. With regard to trans-10,cis-12 CLA, no changes were induced by its addition to the restricted diet. CONCLUSIONS: Insulin function impairment induced by HFHS feeding is not mediated by visfatin and apelin. However, visfatin can play a role in improving insulin sensitivity associated with energy restriction. These results suggest that visfatin may not have evolved as a molecule that reserves the action of insulin when food is widely available, but rather that its function seems to be associated with energy restriction adaptation. In general terms, trans-10,cis-12 CLA did not modify changes induced by energy restriction.

Trans-10, cis-12-conjugated linoleic acid does not increase body fat loss induced by energy restriction.

Very little evidence exists concerning the effects of conjugated linoleic acid (CLA) on body fat reduction induced by energy restriction. Moreover, although an effect of trans-10, cis-12-CLA on lipolysis has been suggested, it has not been consistently shown. The aims of the present study were to determine whether trans-10, cis-12-CLA increases the reduction of body fat induced by energy restriction, and to analyse its effect on lipolysis and adipose tissue lipase expression (hormone-sensitive lipase (HSL) and adipose tissue TAG lipase (ATGL)). Male Syrian Golden hamsters were fed a high-fat diet during 7 weeks in order to make them fatter. Then they were submitted to a mild energy restriction (25 %) without or with supplementation of 0.5 % trans-10, cis-12-CLA for 3 weeks. Basal glycerol release and lipolysis stimulated by several drugs acting at different levels of the lipolytic cascade were measured in epididymal adipose tissue. The expression of HSL and ATGL was assessed by real-time RT-PCR. No differences were found in adipose tissues size between the experimental groups. Medium adipocyte size and total number of adipocytes were similar in both experimental groups. Animals fed the CLA-enriched diet showed similar lipolytic rates as well as HSL and ATGL expressions to the controls. In conclusion, trans-10, cis-12-CLA does not promote adipose tissue lipid mobilisation nor does it heighten body fat reduction induced by energy restriction. Consequently, this CLA isomer does not seem to be a useful tool to be included in body weight-loss strategies followed in obesity treatment.

The role of dietary fat in adipose tissue metabolism.

Energy intake and expenditure tend on average to remain adjusted to each other in order to maintain a stable body weight, which is only likely to be sustained if the fuel mix oxidised is equivalent to the nutrient content of the diet. Whereas protein and carbohydrate degradation and oxidation are closely adjusted to their intakes, fat balance regulation is less precise and that fat is more likely to be stored than oxidised. It has been demonstrated that dietary fatty acids have an influence not only on the fatty acid composition of membrane phospholipids, thus modulating several metabolic processes that take place in the adipocyte, but also on the composition and the quantity of different fatty acids in adipose tissue. Moreover, dietary fatty acids also modulate eicosanoid presence, which have hormone-like activities in lipid metabolism regulation in adipose tissue. Until recently, the adipocyte has been considered to be no more than a passive tissue for storage of excess energy. However, there is now compelling evidence that adipocytes have a role as endocrine secretory cells. Some of the adipokines produced by adipose tissue, such as leptin and adiponectin, act on adipose tissue in an autocrine/paracrine manner to regulate adipocyte metabolism. Furthermore, dietary fatty acids may influence the expression of adipokines. The nutrients are among the most influential of the environmental factors that determine the way adipose tissue genes are expressed by functioning as regulators of gene transcription. Therefore, not only dietary fat amount but also dietary fat composition influence adipose tissue metabolism.