Can Cysteine Metabolism Provide a Target to Treat Obesity?

Framdriftsrapport. Rapporteringsfrist: 20121001. Mottatt: 20130211. 197195 - Can Cysteine Metabolism Provide a Target to Treat Obesity? Side: 8 begrenset. Flere av de beskrevne prosjektene vil nå bli utvidet til også å inkludere aminosyre- og fettsy reprofilen, noe som vil markert heve kvaliteten av prosjektet. 5) Hypotesen om at cystein er viktig for regulering av fettomsetningen har vunnet mer terreng. Dette reflekteres i publiserte oversiktsartikler (Elshorbagy et al) og inviterte foredrag til internasjonale konferanser

BACKGROUND: Obesity within few years will probably become the number one preventable cause of diabetes, cardiovascular disease, cancer, and death. Recently, we discovered a striking relation between the sulphur amino acid cysteine in plasma and body fat m ass: People with high cysteine had 6-10 kg more fat than those with low cysteine. The association was stronger than, and independent of, plasma lipids, energy intake and physical activity. The available data suggest that the association between cysteine a nd fat mass is causal, but we have not identified the mechanism. AIM: Through an international collaborative effort, we wish to uncover the biological mechanisms underlying the association of cysteine with obesity. METHODS: Through cell culture studies, animal experiments, and analyses of data from epidemiological cohorts, we will: 1) Search for the cellular mechanisms linking cysteine to fat mass by investigating the effect of cysteine on mice and human fat cells and fat stem cells 2) Examine whethe r treatment with cysteine-modifying drugs or diets in mice or rats will change body composition, and if so, whether we can relate the findings to changes in plasma biochemistry (glucose, lipid, adipokines, inflammatory markers) and gene expression data in relevant tissues 3) Investigate how cysteine is genetically related to obesity in humans, using genome wide scan data from cohorts with European and Asian participants, i.e., populations with widely different risk of obesity and the related disorders 4) Study the association of cysteine to the fatty acid profiles, inflammatory markers and adipokines in plasma in the general population and in subjects with impaired glucose tolerance or diabetes, to determine if cysteine interferes with fatty acid metabol ism or fat cell endocrine function. These studies may identify how cysteine leads to increased fat accumulation, and thereby provide a powerful new target for prevention and treatment of obesity and overweight.