Annual Report 2011-2012 - Nabi.res.in

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NATIONAL AGRI-FOOD BIOTECHNOLOGY INSTITUTE4. DIET AND HEALTH4.1Effect of dietary constituents onadipogenesis4.1.1Role of arabinoxylans from millets inregulating adipogenesis: A nutrigenomic studyPrincipal Investigator:Kanthi K. KiranCo-Investigator:Mahendra BishnoiIntroduction:Current anti-obesity medications arepharmacological agents which can reduce orcontrol weight. These drugs affect one of thefundamental processes of the weight regulation inhuman body i.e. altering appetite, metabolism orconsumption of calories. There is only one anti-obesity medication, Orlistat, approved by FDA. Itacts through inhibition of pancreatic lipaseenzyme. Rimonabant, acting through blockade ofthe endocannabinoid receptor and Sibutramine,a c t i n g t h r o u g h b r a i n b y i n h i b i t i n gneurotransmitter metabolism were previouslyapproved drugs which have been withdrawn fromthe market in several countries and regionsObesity is a worldwide epidemic and has asignificant negative impact on health, mortalityand related costs. Diet and genetic factorsincluding gene mutations are closely related to thedevelopment of obesity. Untreated, it may lead tochronic diseases, such as diabetes (type II),hypertension, cardiovascular disease and certaintype of cancers. Present anti-obesity medicationsare shown to be associated with side effects uponlong term usage. Phytochemicals such aspolyphenols and non-starch polysaccharides havetremendous health benefits. Arabinoxylans (AXs)are non-starch hemicellulosic polysaccharides,major constituents in the cell walls of cereals andmillets, are reported to have potential healthbenefits in alleviating disease symptoms such asdiabetes, atherosclerosis and colon cancer. WheatAXs help in regulating the weight gain and obesityby controlling the release of gut hormones likepeptide YY and Glucagon-Like Peptide-1(GLP1). The potential beneficial effects of AXsfrom finger millet and kodo millet in regulatingadipogenesis and their metabolic fate in animalmodels will be studied, which is expected toprovide the insight on mechanism of action ofAXs in adipogenesis regulation and help indesigning functional foods with enriched Axs.Research Objectives:llMechanistic studies on the role of AXs onadipogenesis using mouse 3T3-L1 cell linesin-vitro.Modulating adipogenesis and obesity usingAXs in high fat diet induced obese mousemodel through molecular approaches.Long Term Objectives:llTo study the role of high dietary fiberconsumption and the role of gut microbiota inalleviating weight gain and obesity.Designing AXs enriched functional foodmodels that can modulate metabolicdisorders.Research in Progress:Currently, we are standardizing the culturing ofpreadipocytes and differentiation into adipocytes.Primers for important transcriptional factors,enzymes in the fatty acid pathway and keyadipokines are designed. Chemo-enzymaticextraction of AXs from finger millet grains isunder progress.4.1.2 Transient Receptor Potential (TRP)channel mediated modulation of adipogenesisand obesity by dietary moleculesPrincipal Investigator:Mahendra BishnoiCo-Investigator:Kanthi K. KiranIntroduction:31
NATIONAL AGRI-FOOD BIOTECHNOLOGY INSTITUTEincluding India (Banned Medicines, press l To study the effect of dietary modulations ofrelease), Ministry of Health and Family Welfare. TRP channels (TRPV1: capsaicin, capsiate,thFebruary 10 , 2011). The potential side effects piperine; TRPA1: garlic, cinnamon; TRPM8:(increased cardiovascular concerns, stroke, menthol) in a diet (high fat) based in vivosuicidality and depression) of these drugs are mouse model of obesity.much more than their beneficial effects. Over theyears it has been seen that the best and mostLong Term Objectives:effective options available for overweight and l Developing diets constituted of modulatingobese individuals are dieting and physical food components and study their effect onexercise. It is important to have dietary regulations adipogenesis, obesity and relatedto prevent life style problems rather than to search complications.for the treatment. Available literature suggests thatl Special dietary formulations will be madeTransient Receptor Potential (Transient Receptorusing TRP channel modulating dietary agentsPotential Vanilloid (TRPV1), Transient Receptoralone or in combination with other nutrients.Potential Ankyrin (TRPA1), Transient ReceptorPotential Metastatin (TRPM8) channels are l Undertake clinical trial using humanpossible candidates to regulate energy metabolism volunteers for establishing role of TRPand thermogenesis, which can lead to calorie channel modulating dietary agents in obesity.consumption and prevention of obesity. Commondietary spices like chilli pepper, black pepper,Research in Progress:clove, garlic, cinnamon and their constituents Based on our PCR data multiple TRP channel(capsaicin, piperine, eugenol, allicin, genes are expressed in mouse 3T3-L1cinnamaldehyde, menthol) can activate the TRP preadipocytes (high to moderate expression:channels. In this proposal, using the TRP channel TRPP2 (PKD2), TRPC1, TRPV2, TRPM2,receptor system we intend to come up with dietary TRPV4 TRPV1, TRPV3, TRPV6, TRPC4; lowconstituents that can modulate the molecular expression: TRPA1, TRPC6, and TRPM8) andmechanism associated with the process of adipocytes (high to moderate expression: TRPP2adipogenesis, adipose tissue related hormonal (PKD2), TRPV2, TRPC1, TRPV4, TRPM2; lowsecretion and release of pro-inflammatory expression: TRPA1, TRPV3, TRPV6, TRPC4,mediators and lipolysis.TRPV1, TRPC6, and TRPM8) (Table 1). TRPV1,TRPV3, TRPM8, TRPC4, TRPC6 wereResearch Objectives:differential expressed (multiple fold higher inpreadipocytes than adipocytes) (Figure 2).l Determination of expression and function ofTRP channels in commercially availableFurther, these channels are also expressed inmouse preadipocytes cell lines (3T3-L1),murine white adipose tissue (WAT) (high tomoderate expression: TRPP2 (PKD2), TRPV2,human preadipocytes (HPAd) and adipocytesTRPC6, TRPC1, TRPV4, TRPM2, TRPV3,(HAd) cells.TRPC4; low expression: TRPV1, TRPV6,l In-vitro characterization of the molecular TRPM8 and TRPA1] and brown adipose tissuebasis of adipogenesis using mouse/human (BAT) [high to moderate expression: TRPP2gene microarray chip, mouse/human (PKD2), TRPV2, TRPC6, TRPC1, TRPV4,adipogenesis and obesity PCR arrays. TRPM2, TRPV3, TRPC4, TRPV6; low expression:Determination of effect of TRP channel TRPV1, TRPM8, and TRPA1) (Table 1). TRPV4,activation on adipogenesis process in TRPV6 and TRPC6 were differentially expressedmouse/human adipocytes cells.in murine WAT and BAT (Figure 2).32
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Annual Report 2011-2012 - Nabi.res.in

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