In Vitro Screening and Lipid-Lowering Effect of Prickly Pear (Opuntia Ficus-Indica L. Mill.) Fruit Extracts in 3T3-L1 Pre-Adipocytes and Mature Adipocytes.

Opuntia ficus-indica fruits have been widely used due to their nutritional composition and beneficial effects on health, particularly against chronic diseases such as diabetes, obesity, cardiovascular diseases and cancer, among others. In recent years, prickly pear peel and pulp extracts have been characterised, and a high number of bioactive compounds have been identified. This study aimed to analyse the triglyceride-lowering effect of prickly pear peel and pulp extracts obtained from fruits of three varieties (Pelota, Sanguinos, and Colorada) in 3T3-L1 maturing and mature adipocytes. At a concentration of 50 µg/mL, peel extracts from Colorada reduced triglyceride accumulation in pre-adipocytes and mature adipocytes. Additionally, at 25 µg/mL, Pelota peel extract decreased triglyceride content in mature adipocytes. Moreover, maturing pre-adipocytes treated with 50 and 25 µg/mL of Sanguinos pulp extract showed a reduction of triglyceride accumulation. In addition, the lipid-lowering effect of the main individual betalain and phenolic compounds standards were assayed. Piscidic acid and isorhamnetin glycoside (IG2), found in Colorada peel extract, were identified as the bioactive compounds that could contribute more notably to the triglyceride-lowering effect of the extract. Thus, the betalain and phenolic-rich extracts from Opuntia ficus indica fruits may serve as an effective tool in obesity management.

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss.

BACKGROUND: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. AIM: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). MATERIALS AND METHODS: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. RESULTS: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. CONCLUSION: Obesity-related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.

Sexual Dimorphism in Brown Adipose Tissue Activation and White Adipose Tissue Browning.

The present narrative review gathers the studies reported so far, addressing sex differences in the effects of cold exposure, feeding pattern and age on brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. In rodents, when exposed to decreasing temperatures, females activate thermogenesis earlier. Results obtained in humans go in the same line, although they do not provide results as solid as those obtained in rodents. Regarding the effects of overfeeding, interesting sex differences on BAT thermogenic capacity have been reported, and the greater or lower sensitivity of each sex to this dietary situation seems to be dependent on the type of feeding. In the case of energy restriction, females are more sensitive than males. In addition, sex differences have also been observed in thermogenesis changes induced by phenolic compound administration. During sexual development, an increase in BAT mass and BAT activity takes place. This phenomenon is greater in boys than in girls, probably due to its relation to muscle-mass growth. The opposite situation takes place during ageing, a lifespan period where thermogenic capacity declines, this being more acute in men than in women. Finally, the vast majority of the studies have reported a higher susceptibility to developing WAT browning amongst females. The scarcity of results highlights the need for further studies devoted to analysing this issue, in order to provide valuable information for a more personalised approach.

Usefulness of Probiotics in the Management of NAFLD: Evidence and Involved Mechanisms of Action from Preclinical and Human Models.

The present review aims at analyzing the current evidence regarding probiotic administration for non-alcoholic fatty liver disease (NAFLD) management. Additionally, the involved mechanisms of action modulated by probiotic administration, as well as the eventual limitations of this therapeutic approach and potential alternatives, are discussed. Preclinical studies have demonstrated that the administration of single-strain probiotics and probiotic mixtures effectively prevents diet-induced NAFLD. In both cases, the magnitude of the described effects, as well as the involved mechanisms of action, are comparable, including reduced liver lipid accumulation (due to lipogenesis downregulation and fatty acid oxidation upregulation), recovery of gut microbiota composition and enhanced intestinal integrity. Similar results have also been reported in clinical trials, where the administration of probiotics proved to be effective in the treatment of NAFLD in patients featuring this liver condition. In this case, information regarding the mechanisms of action underlying probiotics-mediated hepatoprotective effects is scarcer (mainly due to the difficulty of liver sample collection). Since probiotics administration represents an increased risk of infection in vulnerable subjects, much attention has been paid to parabiotics and postbiotics, which seem to be effective in the management of several metabolic diseases, and thus represent a suitable alternative to probiotic usage.

Anti-Obesity Effects of Isorhamnetin and Isorhamnetin Conjugates.

Isorhamnetin is a plant-derived secondary metabolite which belongs to the family of flavonoids. This review summarises the main outcomes described in the literature to date, regarding the effects of isorhamnetin on obesity from in vitro and in vivo studies. The studies carried out in pre-adipocytes show that isorhamnetin is able to reduce adipogenesis at 10 µM or higher doses and that these effects are mediated by Pparγ and by Wnt signalling pathway. Very few studies addressed in rodents are available so far. It seems that treatment periods longer than two weeks are needed by isorhamnetin and its glycosides to be effective as anti-obesity agents. Nevertheless, improvements in glycaemic control can be observed even in short treatments. Regarding the underlying mechanisms of action, although some contradictory results have been found, reductions in de novo lipogenesis and fatty acid uptake could be proposed. Further research is needed to increase the scientific evidence referring to this topic; studies in animal models are essential, as well as randomised clinical trials to determine whether the positive results observed in animals could also be found in humans, in order to determine if isorhamnetin and its glycosides can represent a real tool against obesity.

Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity.

BACKGROUND/OBJECTIVES: Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at: (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs). SUBJECTS/METHODS: Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery. RESULTS: Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery. CONCLUSIONS: Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.

An energy restriction-based weight loss intervention is able to reverse the effects of obesity on the expression of liver tumor-promoting genes.

The epidemiological evidence regarding the association of obesity with liver disease and possibly hepatocellular carcinoma highlights the need for investigations of whether obesity itself could induce the differential expression of genes commonly associated with the initial phase of liver tumorigenesis, and whether such phenomenon could be reversed after a weight loss intervention. In this study, obese Zucker rats were found to have dysregulated cell proliferation, antioxidative defenses, and tumor suppressor gene expression in association with liver dysfunction parameters, as well as oxidative stress and inflammation. Importantly, after a 4-week weight loss protocol of energy restriction and/or exercise, this effect on the liver carcinogenesis-related genes was reversed concomitantly with reductions in the fat mass, hepatic lipid content, oxidative stress, and inflammation. The findings indicate that the oxidative stress and inflammation associated with excess adiposity promote dysregulation of the genes involved in liver tumorigenesis. This is clinically relevant because these effects were detectable in the liver without evidence of a tumoral mass and were reversed after weight loss. Consequently, this study reveals the susceptibility of obese individuals to the initiation of a hepatocarcinogenic process, and how this can be prevented by achieving a healthy body weight.

An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity.

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

Effects of Physiological Doses of Resveratrol and Quercetin on Glucose Metabolism in Primary Myotubes.

Phenolic compounds have emerged in recent years as an option to face insulin resistance and diabetes. The central aim of this study was: (1) to demonstrate that physiological doses of resveratrol (RSV) or quercetin (Q) can influence glucose metabolism in human myotubes, (2) to establish whether AMP-activated protein kinase (AMPK) and protein kinase B -PKB- (Akt) pathways are involved in this effect. In addition, the effects of these polyphenols on mitochondrial biogenesis and fatty acid oxidation were analysed. Myotubes from healthy donors were cultured for 24 h with either 0.1 µM of RSV or with 10 µM of Q. Glucose metabolism, such as glycogen synthesis, glucose oxidation, and lactate production, were measured with D[U-14C]glucose. ß-oxidation using [1-14C]palmitate as well as the expression of key metabolic genes and proteins by Real Time PCR and Western blot were also assessed. Although RSV and Q increased pgc1α expression, they did not significantly change either glucose oxidation or ß-oxidation. Q increased AMPK, insulin receptor substrate 1 (IRS-1), and AS160 phosphorylation in basal conditions and glycogen synthase kinase 3 (GSK3ß) in insulin-stimulated conditions. RSV tended to increase the phosphorylation rates of AMPK and GSK3ß. Both of the polyphenols increased insulin-stimulated glycogen synthesis and reduced lactate production in human myotubes. Thus, physiological doses of RSV or Q may exhibit anti-diabetic actions in human myotubes.

Effects of Quercetin Metabolites on Triglyceride Metabolism of 3T3-L1 Preadipocytes and Mature Adipocytes.

Quercetin (Q) has rapid metabolism, which may make it worthwhile to focus on the potential activity of its metabolites. Our aim was to evaluate the triglyceride-lowering effects of Q metabolites in mature and pre-adipocytes, and to compare them to those induced by Q. 3T3-L1 mature and pre-adipocytes were treated with 0.1, 1 and 10 µM of Q, tamarixetin (TAM), isorhamnetin (ISO), quercetin-3-O-glucuronide (3G), quercetin-3-O-sulfate (3S), as well as with 3S and quercetin-4-O-sulfate (4S) mixture (3S+4S). Triglyceride (TG) content in both cell types, as well as free fatty acid (FFA) and glycerol in the incubation medium of mature adipocytes were measured spectrophotometrically. Gene expression was assessed by RT-PCR. In mature adipocytes, Q decreased TG at 1 and 10 µM, 3S metabolite at 1 and 10 µM, and 3S+4S mixture at 10 µM. 3S treatment modified the glucose uptake, and TG assembling, but not lipolysis or apoptosis. During differentiation, only 10 µM of ISO reduced TG content, as did Q at physiological doses. In conclusion, 3S metabolite but not ISO, 3G, 4S and TAM metabolites can contribute to the in vivo delipidating effect of Q.

Anti-Obesity Effects of Microalgae.

In recent years, microalgae have attracted great interest for their potential applications in nutraceutical and pharmaceutical industry as an interesting source of bioactive medicinal products and food ingredients with anti-oxidant, anti-inflammatory, anti-cancer, and anti-microbial properties. One potential application for bioactive microalgae compounds is obesity treatment. This review gathers together in vitro and in vivo studies which address the anti-obesity effects of microalgae extracts. The scientific literature supplies evidence supporting an anti-obesity effect of several microalgae: Euglena gracilis, Phaeodactylum tricornutum, Spirulina maxima, Spirulina platensis, or Nitzschia laevis. Regarding the mechanisms of action, microalgae can inhibit pre-adipocyte differentiation and reduce de novo lipogenesis and triglyceride (TG) assembly, thus limiting TG accumulation. Increased lipolysis and fatty acid oxidation can also be observed. Finally, microalgae can induce increased energy expenditure via thermogenesis activation in brown adipose tissue, and browning in white adipose tissue. Along with the reduction in body fat accumulation, other hallmarks of individuals with obesity, such as enhanced plasma lipid levels, insulin resistance, diabetes, or systemic low-grade inflammation are also improved by microalgae treatment. Not only the anti-obesity effect of microalgae but also the improvement of several comorbidities, previously observed in preclinical studies, has been confirmed in clinical trials.

Potential Usefulness of a Wakame/Carob Functional Snack for the Treatment of Several Aspects of Metabolic Syndrome: From In Vitro to In Vivo Studies.

Metabolic syndrome (MetS) greatly increases the risk of cardiovascular diseases and type 2 diabetes mellitus. The aim of this study was to evaluate the efficacy of functional snacks containing a combination of wakame (W) and carob pod (CP) flours in reducing markers associated with MetS. The mechanisms of action underlying these effects were also evaluated. In vitro approaches were carried out in mature 3T3-L1 adipocytes and RAW 264.7 macrophages treated with different doses of extracts from W, CP, or a combination of both. Furthermore, an in vivo experiment was conducted in rats with MetS treated with normal-caloric diets containing different snack formulations with combinations of 1/50 (snack A) or 1/5 of wakame/carob (snack B). In vitro experiments results indicated that both W and CP had delipidating effects, but only the latter induced anti-inflammatory and anti-hypertensive effects. As far as the in vivo study is concerned, snack B was ineffective and snack A showed an anti-hypertensive effect in rats with MetS. The present study shows for the first time the in vitro efficacy of a W and CP combination as an anti-inflammatory, delipidating, and anti-hypertensive tool, and its potential usefulness in treating MetS.

Resveratrol and Pterostilbene, Two Analogue Phenolic Compounds, Affect Aquaglyceroporin Expression in a Different Manner in Adipose Tissue.

Aquaglyceroporins (AQPs) are transmembrane channels that mediate glycerol release and glycerol uptake. They are involved in fat metabolism, with implications in obesity. The aim was to determine whether the administration of resveratrol and pterostilbene during the six weeks of the experimental period would modify AQPs expression in white and brown adipose tissues from Wistar rats fed an obesogenic diet, and to establish a potential relationship with the delipidating properties of these compounds. Consequently, thirty-six rats were divided into four groups: (a) group fed a standard diet; and three more groups fed a high-fat high-sucrose diet: (b) high-fat high-sucrose group: (c) pterostilbene-treated group (30 mg/kg/d): (d) resveratrol-treated group (30 mg/kg/d). Epididymal, subcutaneous white adipose tissues and interscapular brown adipose tissue were dissected. AQPs gene expression (RT-PCR) and protein expression (western-blot) were measured. In white adipose tissue, pterostilbene reduced subcutaneous adipose tissue weight and prevented the decrease in AQP9 induced by obesogenic feeding, and thus glycerol uptake for triglyceride accumulation. Resveratrol reduced epididymal adipose tissue weight and avoided the decrease in AQPs related to glycerol release induced by high-fat high-sucrose feeding, suggesting the involvement of lipolysis in its body-fat lowering effect. Regarding brown adipose tissue, AQP7 seemed not to be involved in the previously reported thermogenic activity of both phenolic compounds.

Involvement of 5'-Activated Protein Kinase (AMPK) in the Effects of Resveratrol on Liver Steatosis.

This review focuses on the role of 5'-activated protein kinase (AMPK) in the effects of resveratrol (RSV) and some RSV derivatives on hepatic steatosis. In vitro studies, performed in different hepatic cell models, have demonstrated that RSV is effective in preventing liver TG accumulation by activating AMPK, due to its phosphorylation. These preventive effects have been confirmed in studies conducted in animal models, such as mice and rats, by administering the phenolic compound at the same time as the diet which induces TG accumulation in liver. The literature also includes studies focused on other type of models, such as animals showing alcohol-induced steatosis or even steatosis induced by administering chemical products. In addition to the preventive effects of RSV on hepatic steatosis, other studies have demonstrated that it can alleviate previously developed liver steatosis, thus its role as a therapeutic tool has been proposed. The implication of AMPK in the delipidating effects of RSV in in vivo models has also been demonstrated.

Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes.

BACKGROUND: Adipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured. METHODS: Pre-adipocytes were cultured from day 0 to day 8 and mature adipocytes for 48 h with the polyphenols at doses of 1, 10 and 25 µM. RESULTS: Apigenin did not show an anti-adipogenic action. Pre-adipocytes treated with hesperidin and kaempferol showed reduced TG content at the three experimental doses. Apigenin did not modify the expression of the main adipogenic genes (c/ebpß, c/ebpα, pparγ and srebp1c), hesperidin inhibited genes involved in the three phases of adipogenesis (c/ebpß, srebp1c and perilipin) and kaempferol reduced c/ebpß. In mature adipocytes, the three polyphenols reduced TG accumulation at the dose of 25 µM, but not at lower doses. All compounds increased mRNA levels of atgl. Apigenin and hesperidin decreased fasn expression. The present study shows the anti-adipogenic effect and delipidating effects of apigenin, hesperidin and kaempferol in human adipocytes derived from hMSCs. While hesperidin blocks all the stages of adipogenesis, kaempferol only inhibits the early stage. Regarding mature adipocytes, the three compounds reduce TG accumulation by activating, at least in part, lipolysis, and in the case of hesperidin and apigenin, also by reducing lipogenesis. CONCLUSIONS: The present study shows for the first time the anti-adipogenic effect and delipidating effect of apigenin, hesperidin and kaempferol in human adipocytes derived from MSCs for the first time.

Low Oxygen Consumption is Related to a Hypomethylation and an Increased Secretion of IL-6 in Obese Subjects with Sleep Apnea-Hypopnea Syndrome.

BACKGROUND: Deoxyribonucleic acid (DNA) methylation is an epigenetic modification involved in gene expression regulation, usually via gene silencing, which contributes to the risks of many multifactorial diseases. The aim of the present study was to analyze the influence of resting oxygen consumption on global and gene DNA methylation as well as protein secretion of inflammatory markers in blood cells from obese subjects with sleep apnea-hypopnea syndrome (SAHS). METHODS: A total of 44 obese participants with SAHS were categorized in 2 groups according to their resting oxygen consumption. DNA methylation levels were evaluated using a methylation-sensitive high resolution melting approach. RESULTS: The analyzed interleukin 6 (IL6) gene cytosine phosphate guanine (CpG) islands showed a hypomethylation, while serum IL-6 was higher in the low compared to the high oxygen consumption group (p < 0.05). Moreover, an age-related loss of DNA methylation of tumor necrosis factor (B = -0.82, 95% CI -1.33 to -0.30) and long interspersed nucleotide element 1 (B = -0.46; 95% CI -0.87 to -0.04) gene CpGs were found. Finally, studied CpG methylation levels of serpin peptidase inhibitor, clade E member 1 (r = 0.43; p = 0.01), and IL6 (r = 0.41; p = 0.02) were positively associated with fat-free mass. CONCLUSIONS: These findings suggest a potential role of oxygen in the regulation of inflammatory genes. Oxygen consumption measurement at rest could be proposed as a clinical biomarker of metabolic health.

Anti-Inflammatory Effects of the Mediterranean Diet in the Early and Late Stages of Atheroma Plaque Development.

Objective. To evaluate the long-term effects of a Mediterranean diet (MeDiet) intervention on the plasma concentrations of inflammatory and plaque stability-related molecules in elderly people at high risk for cardiovascular disease. Design and Setting. 66 participants from primary care centers affiliated with the Hospital Clinic of Barcelona were randomized into 3 groups: MeDiet plus extra virgin olive oil (EVOO) or nuts and a low-fat diet (LFD). At baseline and at 3 and 5 years, we evaluated the changes in the plasma concentrations of 24 inflammatory biomarkers related to the different stages of the atherosclerotic process by Luminex®. Results. At 3 and 5 years, both MeDiet groups showed a significant reduction of IL-6, IL-8, MCP-1, and MIP-1ß (P < 0.05; all) compared to LFD. IL-1ß, IL-5, IL-7, IL-12p70, IL-18, TNF-α, IFN-γ, GCSF, GMCSF, and ENA78 (P < 0.05; all) only decreased in the MeDiet+EVOO group and E-selectin and sVCAM-1 (P < 0.05; both) in the MeDiet+nuts group. Conclusions. Long-term adherence to MeDiet decreases the plasma concentrations of inflammatory biomarkers related to different steps of atheroma plaque development in elderly persons at high cardiovascular risk.

Pterostilbene Inhibits Lipogenic Activity similar to Resveratrol or Caffeine but Differently Modulates Lipolysis in Adipocytes.

The anti-obesity effects of resveratrol shown in rodents are not transposed into an efficient therapy of human obesity. Consequently, the search for molecules mimicking or surpassing resveratrol actions is ongoing. The natural phenolic compound pterostilbene exhibits beneficial health effects and has the capacity to limit fat mass in animal models. In this study, we tested whether pterostilbene modulates triacylglycerol accumulation/breakdown. Prolonged exposure to pterostilbene or resveratrol inhibited adipocyte differentiation in 3T3-F442A preadipocytes. Acute effects on lipolysis, antilipolysis and lipogenesis were determined for pterostilbene in mouse adipocytes, and compared with resveratrol. Pterostilbene was also tested on glycerol release and glucose uptake in subcutaneous human adipocytes. Dose-response analyses did not reveal a clear lipolytic effect in both species. The antilipolytic effect of insulin was improved by pterostilbene at 1-10 µM in mouse fat cells only, while at 1 mM, the phenolic compound was antilipolytic in human fat cells in a manner not additive to insulin. Pterostilbene dose-dependently inhibited glucose incorporation into lipids similarly to resveratrol and caffeine. However, only the former did not inhibit insulin-stimulated glucose uptake. Indeed, pterostilbene abolished the insulin lipogenic effect without inhibiting its antilipolytic action and rapid activation of glucose uptake. Pterostilbene therefore exhibits a unique panel of direct interactions with adipocytes that relies on its reported anti-obesity and antidiabetic properties. Copyright © 2017 John Wiley & Sons, Ltd.

Role of Omentin, Vaspin, Cardiotrophin-1, TWEAK and NOV/CCN3 in Obesity and Diabetes Development.

Adipose tissue releases bioactive mediators called adipokines. This review focuses on the effects of omentin, vaspin, cardiotrophin-1, Tumor necrosis factor-like Weak Inducer of Apoptosis (TWEAK) and nephroblastoma overexpressed (NOV/CCN3) on obesity and diabetes. Omentin is produced by the stromal-vascular fraction of visceral adipose tissue. Obesity reduces omentin serum concentrations and adipose tissue secretion in adults and adolescents. This adipokine regulates insulin sensitivity, but its clinical relevance has to be confirmed. Vaspin is produced by visceral and subcutaneous adipose tissues. Vaspin levels are higher in obese subjects, as well as in subjects showing insulin resistance or type 2 diabetes. Cardiotrophin-1 is an adipokine with a similar structure as cytokines from interleukin-6 family. There is some controversy regarding the regulation of cardiotrophin-1 levels in obese -subjects, but gene expression levels of cardiotrophin-1 are down-regulated in white adipose tissue from diet-induced obese mice. It also shows anti-obesity and hypoglycemic properties. TWEAK is a potential regulator of the low-grade chronic inflammation characteristic of obesity. TWEAK levels seem not to be directly related to adiposity, and metabolic factors play a critical role in its regulation. Finally, a strong correlation has been found between plasma NOV/CCN3 concentration and fat mass. This adipokine improves insulin actions.

Resveratrol-Induced Effects on Body Fat Differ Depending on Feeding Conditions.

Science constantly seeks to identify new molecules that could be used as dietary functional ingredients in the fight against obesity and its co-morbidities. Among them, polyphenols represent a group of molecules of increasing interest. One of the most widely studied polyphenols is resveratrol (trans-3,4',5-trihydroxystilbene), which has been proposed as an "energy restriction mimetic" because it can exert energy restriction-like effects. The aim of this review is to analyze the effects of resveratrol on obesity under different feeding conditions, such as overfeeding, normal feeding, and energy restriction, in animals and humans. The vast majority of the studies reported have addressed the administration of resveratrol to animals alongside an obesogenic diet. Under these experimental conditions usually a decreased body weight amount was found. To date, studies that focus on the effects of resveratrol under normal feeding or energy restriction conditions in animals and humans are scarcer. In these studies no changes in body fat were reported. After analyzing the results obtained under overfeeding, normal feeding, and energy restriction conditions, it can be stated that resveratrol is useful in reducing body fat accumulation, and thus preventing obesity. Nevertheless, for ethical reasons, these results have been obtained in animals. By contrast, there are no evidences showing the usefulness of this phenolic compound in reducing previously accumulated body fat. Consequently, as of yet, there is not scientific support for proposing resveratrol as a new anti-obesity treatment tool.