George, T. | Search bioRxiv

bioRxiv2018

Genome wide association study of body weight, body mass index, adiposity, and fasting glucose in 3,173 outbred rats

Objective Obesity is influenced by genetic and environmental factors. Despite success of human genome wide association studies (GWAS), the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify genetic loci underlying obesity and related morphometric and metabolic traits.Methods We measured obesity-relevant traits including body weight, body length, body mass index, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat GWAS to date. Genetic loci were identified using a linear mixed model that accounted for the complex family relationships of the HS and covariate to account for differences among the three phenotyping centers.Results We identified 32 independent loci, several of which contained only a single gene (e.g. Epha5, Nrg1 and Klhl14) or obvious candidate genes (Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity-related traits, and extensive pleiotropy at individual loci.Conclusions These studies demonstrate utility of HS rats for investigating the genetics of obesity related traits across institutions and identify several candidate genes for future functional testing.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genetics↗

bioRxiv2018

Ameliorative potential of curcumin on cigarette smoke extract induced cognitive impairment in zebrafish

Curcumin is a major phyto-constituent of Curcuma longa. It has been reported that it that it showed various pharmacological actions via anti-oxidant, anti-inflammatory, and immunomodulatory actions. The present study undergoes the therapeutic evaluation of curcumin in cigarette smoke extract (CSE) exposure induced cognitive impairment in zebrafish. Methods: The cognitive impairment was induced by exposure to 25 ml of 200 % CSE; 10 minutes/day, for 7 consecutive days. The pre-treatment of curcumin (10 and 20 mg/kg) and montelukast(20 mg/kg) were exposed in 25 ml drug solution (10 minutes/day for 10 consecutive days). The changes of CSE induced cognitive dysfunction were evaluated by using different test methods such as colour recognition test; partition preference test; horizontal compartment test; and T-Maze tests. Further, the CSE exposure induced changes of biochemical parameters i.e., acetylcholinesterase activity; lipid peroxidation; reduced glutathione; and total protein levels were estimated in the brain of zebrafish. The pre-exposure of curcumin shown to produce the ameliorative effect against CSE induced neurocognitive impairments along with alteration of biochemical changes. Theseresults were comparable to reference control i.e., montelukast pre-treated group. Therefore, the curcumin can be served as newer medicines for immunological reaction associated neurocognitive disorders like Alzheimer and multiple sclerosis due to its potential anti-oxidative; anti-inflammatory; immunomodulatory; and acetylcholinesterase inhibitory actions.\n\nSUMMARYLoss of memory is a major problem in old age population. Curcumin used to treats the various neurological disorders. Curcumin possess the ameliorative potential in toxin induced neurocognitive function.

animal behavior and cognition↗