Editorial: diet, inflammation and colorectal cancer

This Research Topic was designed to provide the reader with an overview of the impact of body weight and adiposity, as well as of specific food compounds on the inflammatory status in health and disease states, such as CRC. We collected original and review articles featuring the role of specific food compounds in the regulation of immune response and their potential therapeutic implications, the effect of polyunsaturated fatty acids (PUFA), oligosaccharides, polyphenols and body weight in the modulation of inflammation and long-term disease outcomes, highlighting the link between diet, inflammation, and CRC

Down-regulation of heart HFABP and UCP2 gene expression in diet-induced (cafeteria) obese rats.

Long-term exposure to hypercaloric high fat diet induced marked tissue fatty acid accumulation and may influence cell function. Previous results in our laboratory showed that uncoupling proteins (UCPs) and fatty acid-binding protein (FABP) gene expression are changed in adipose tissue and skeletal muscle tissue in diet-induced (cafeteria) obese animals. The aim of this study was to examine heart FABP (HFABP) and UCP2 gene expressions in dietary obese rats. Rats fed on a high-fat diet for 65 days had significantly higher fat stores and body weight than control rats. Interestingly, we found that both HFABP and UCP2 mRNA levels were significantly reduced in cafeteria-obese rats when compared to control animals. Moreover, a statistically significant correlation was observed between the two gene expression levels. The down-regulation of heart HFABP and UCP2 parallels the lower lipid utilization which may account for an enhanced fat deposition. It is plausible that these two genes are regulated by the same family of transcription factors

Avances en nutrición molecular: nutrigenómica y/o nutrigenética

La aplicación de las técnicas de la biología molecular y el éxito del Proyecto Genoma Humano ha abierto una nueva era tanto en Medicina como en Nutrición. Hasta la fecha, al menos, 1.000 genes humanos causantes de enfermedades han sido identificados y parcialmente caracterizados, el 97% de los cuales sabemos ahora que son causantes de enfermedades monogénicas. Sin embargo, otras patologías como la obesidad, enfermedad cardiovascular, diabetes, cáncer se deben a complejas interacciones entre diversos genes y factores ambientales. A pesar de los numerosos estudios de asociación, más de 600 publicados desde 2002, la base molecular de las enfermedades crónicas es todavía incierta. La información sobre polimorfismos de nucleótidos y mapas de haplotipos son recursos adicionales para identificar genes involucrados en enfermedades. El desarrollo genómico se aproxima, sin embargo, no se conocen con precisión algunos componentes de la dieta y sus mecanismos, que influyen de forma importante en la expresión de la información genética y en las alteraciones patológicas. La industria alimentaria tiene la oportunidad de utilizar los componentes bioactivos de los alimentos para mejorar la salud y evitar las enfermedades teniendo en cuenta la constitución genética de los consumidores. Esta nueva era de la nutrición molecular —interacciones genes-nutrientes— puede crecer en diversas direcciones, aunque hay dos esenciales. De una parte, el estudio de la influencia de los nutrientes sobre la expresión de genes (nutrigenómica) y de otra conocer la influencia de las variaciones genéticas en la respuesta del organismo a los nutrientes (nutrigenética)

A dysregulation in CES1, APOE and other lipid metabolism-related genes is associated to cardiovascular risk factors linked to obesity

OBJECTIVE: The aim of the present study was to investigate the relationship between the differential expression of genes related to lipid metabolism in subcutaneous adipose tissue and metabolic syndrome features in lean and obese subjects with habitual high fat intake. METHODS: Microarray and RT-PCR analysis were used to analyze and validate differential gene expression in subcutaneous abdominal adipose tissue samples from lean and obese phenotype subjects. RESULTS: Several genes and transcripts involved in lipolysis were down-regulated, such as AKAP1, PRKAR2B, Gi and CIDEA, whereas NPY1R and CES1 were up-regulated, when comparing obese to lean subjects. Similarly, transcripts associated with cholesterol and lipoprotein metabolism showed a differential expression, with APOE and ABCA being decreased and VLDLR being increased in obese versus lean subjects. In addition, positive correlations were found between different markers of the metabolic syndrome and CES1 and NPY1R mRNA expressions, while APOE showed an inverse association with some of them. CONCLUSION: Different expression patterns in transcripts encoding for proteins involved in lipolysis and lipoprotein metabolism were found between lean and obese subjects. Moreover, the dysregulation of genes such as CES1 and APOE seems to be associated with some physiopathological markers of insulin resistance and cardiovascular risk factors in obesity

Genetics of obesity.

OBJECTIVE: The aim was to review and update advances in genetics of obesity. DESIGN: Analysis and interpretation of recent investigations about regulating the energy balance as well as about gene-nutrient interactions and current nutri-genomic research methods. BACKGROUND AND MAIN STATEMENTS: Obesity results from a long-term positive energy balance. However, its rising prevalence in developed and developing societies must reflect lifestyle changes, since genetic susceptibility remains stable over many generations. Like most complex diseases, obesity derives from a failure of adequate homoeostasis within the physiological system controlling body weight. The identification of genes that are involved in syndromic, monogenic and polygenic obesity has seriously improved our knowledge of body weight regulation. This disorder may arise from a deregulation at the genetic level (e.g. gene transcription or altered protein function) or environmental exposure (e.g. diet, physical activity, etc.). CONCLUSIONS: In practice, obesity involves the interaction between genetic and environmental factors

Effects of Trecadrine, a beta3-adrenergic agonist, on leptin secretion, glucose and lipid metabolism in isolated rat adipocytes

Objective: Leptin, a hormone produced in adipocytes, is a key signal in the regulation of food intake and energy expenditure. beta-Adrenergic agonists have been shown to inhibit leptin gene expression and leptin secretion. The mechanisms underlying the inhibitory effects of beta-adrenergic agonists have not been established. In this study, we examined the effects of TrecadrineÒ, a novel beta3-adrenergic agonist, on basal and insulin-stimulated leptin secretion in isolated rat adipocytes. Because insulin-stimulated glucose metabolism is an important regulator of leptin expression and secretion by the adipocytes, the effects of Trecadrine on indices of adipocyte metabolism were also examined. Measurements: Isolated adipocytes were incubated with Trecadrine (10-8-10-4 M) in the absence or presence of insulin (1.6 nM). Leptin secretion, glucose utilization, lactate production, glucose incorporation into CO2 and triglyceride, as well as lipolysis (glycerol release) were determined. Results: Trecadrine induced a concentration-dependent inhibition of basal leptin secretion. Trecadrine also decreased insulin-stimulated leptin secretion; however, the effect was not as pronounced as in the absence of insulin. Treatment of adipocytes with Trecadrine increased basal glucose utilization and produced a further increase in insulin-stimulated glucose utilization. Basal lactate production was also increased by Trecadrine; however, the proportion (percentage) of glucose carbon released as lactate was unaffected. In the presence of insulin, absolute lactate production was unaffected by Trecadrine at 96 h. However, the percentage of glucose carbon released as lactate was significantly decreased by insulin treatment, and was further decreased by the co-treatment with Trecadrine. Trecadrine induced a dose-dependent increase of the absolute amount of glucose incorporated into triglyceride. However, the percentage of glucose utilized that was incorporated into triglyceride was unaffected by Trecadrine. Trecadrine did not modify the proportion of glucose utilized that was oxidized to CO2. Trecadrine increased glycerol release after 96 h of treatment. Glycerol release was negatively correlated with leptin secretion. Conclusions: These results suggest that alterations of glucose metabolism are not directly involved in the effects of beta3-adrenergic agonists to inhibit leptin expression and secretion. The inverse relationship between leptin secretion and the increase of glycerol levels, which is an index of the activation of cAMP-dependent protein kinases, suggests that activation of the cAMP signaling pathway mediates the inhibitory effects of Trecadrine on leptin gene expression and secretion

Obesidad, inflamación e insulino-resistencia: papel de los ligandos del receptor gp 130

Obesity can be considered as a low grade inflammatory disease, characterized by increased plasma levels of proinflammatory cytokines such as tumoral necrosis factor-a (TNF-a), and acute phase reactant proteins like C-reactive protein. In this context, some cytokines of the interleukin-6 (IL-6) family have been involved in the inflammatory processes associated to obesity. In addition to IL-6, the IL-6 cytokine family includes IL-11, ciliary neurotrophic factor (cntf), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF) y Oncostatin M (OsM). These proteins are also known as gp130 cytokines because all of them exert their action via the glycoprotein 130 (gp130) as a common transducer protein within their functional receptor complexes. However, their role in obesity and related disorders is controversial; thus, whereas some studies have described the involvement of gp130 cytokines in the development of obesity and its related cluster of pathophysiologic conditions like insulin-resistance, fatty liver and cardiovascular diseases, other trials have proposed the gp130 receptor ligands as therapeutic targets in the treatment of obesity and its related disorders. In fact, CNTF treatment has demonstrated to be effective in the reduction of body weight, by promoting the inhibition of food intake and the activation of the energy expenditure, together with an improvement of insulin sensitivity. This review analyzes the potential therapeutic role of some of the gp130 ligands in obesity and related diseases

Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes

Visfatin is an adipokine highly expressed in visceral AT (adipose tissue) of humans and rodents, the production of which seems to be dysregulated in excessive fat accumulation and conditions of insulin resistance. EPA (eicosapentaenoic acid), an n−3 PUFA (polyunsaturated fatty acid), has been demonstrated to exert beneficial effects in obesity and insulin resistance conditions, which have been further linked to its reported ability to modulate adipokine production by adipocytes. TNF-α (tumour necrosis factor-α) is a pro-inflammatory cytokine whose production is increased in obesity and is involved in the development of insulin resistance. Control of adipokine production by some insulin-sensitizing compounds has been associated with the stimulation of AMPK (AMP-activated protein kinase). The aim of the present study was to examine in vitro the effects of EPA on visfatin production and the potential involvement of AMPK both in the absence or presence of TNF-α. Treatment with the pro-inflammatory cytokine TNF-α (1 ng/ml) did not modify visfatin gene expression and protein secretion in primary cultured rat adipocytes. However, treatment of these primary adipocytes with EPA (200 μmol/l) for 24 h significantly increased visfatin secretion (P<0.001) and mRNA gene expression (P<0.05). Moreover, the stimulatory effect of EPA on visfatin secretion was prevented by treatment with the AMPK inhibitor Compound C, but not with the PI3K (phosphoinositide 3-kinase) inhibitor LY294002. Similar results were observed in 3T3-L1 adipocytes. Moreover, EPA strongly stimulated AMPK phosphorylation alone or in combination with TNF-α in 3T3-L1 adipocytes and pre-adipocytes. The results of the present study suggest that the stimulatory action of EPA on visfatin production involves AMPK activation in adipocytes

Effects of eicosapentaenoic acid ethyl ester on visfatin and apelin in lean and overweight (cafeteria diet-fed) rats

Previous studies have demonstrated that the n-3 fatty acid EPA improves insulin resistance induced by high-fat diets. The aim of the present study was to investigate the potential role of visfatin and apelin in the insulin-sensitising effects of EPA ethyl ester. The effects of EPA on muscle and adipose GLUT mRNA, as well as on liver glucokinase (GK) and glucose-6-phosphatase (G6Pase) activity, were investigated. Male Wistar rats fed on a standard diet or a high-fat cafeteria diet were daily treated by oral administration with EPA ethyl ester (1 g/kg) for 5 weeks. A significant decrease (P,0·01) in white adipose tissue (WAT) visfatin mRNA levels was found in the cafeteria-fed rats, which was reversed by EPA administration (P,0·05). Moreover, a negative relationship was observed between homeostatic model assessment (HOMA) and the visfatin:total WAT ratio. In contrast, cafeteria-diet feeding caused a significant increase (P,0·01) in apelin mRNA in visceral WAT. EPA increased (P,0·01) apelin gene expression, and a negative relationship between HOMA index with visceral apelin mRNA and serum apelin:total WAT ratio was also observed. EPA treatment did not induce changes in skeletal muscle GLUT1, GLUT4 or insulin receptor mRNA levels. Neither liver GK and G6Pase activity nor the GK:G6Pase ratio was modified by EPA. These data suggest that somehow the insulin-sensitising effects of EPA could be related to its stimulatory action on both visfatin and apelin gene expression in visceral fat, while changes in skeletal muscle GLUT, as well as in hepatic glucose production, are not likely to be the main contributing factors in the improvement in insulin resistance induced by EPA