The BCM Nutrition and Obesity Pilot and Feasibility Fund (P&F) Program is accepting proposals for one‑year grants of up to $25,000 total direct cost to support projects in nutrition or obesity research. P&F projects may be biomedical, epidemiological, community-based, or clinical. They may include laboratory or non-laboratory research projects that focus either on human nutrition, animal studies, or cell-based research related to nutrition or obesity.
Eligibility: Applicants must be full-time faculty members at Baylor College of Medicine. Applications are encouraged from early-career investigators and from established investigators not currently working in the obesity and nutrition fields.
Review Process: Proposals will be reviewed and rated by CRON faculty with appropriate expertise.
Criteria for Awards: The evaluation criteria will be:
- Relevance to obesity or nutrition research
- Probability of leading to a successfully funded external grant application.
Deadline for Submission: 2020 competition will be announced later this year.
We have recently completed our first funding cycle. Two awardees were announced and funded for $20,000 for one year.
Kangho Kim, Ph.D. – “Molecular Characterization of Hepatokine ORM2 in Obesity”
Emerging evidence indicates that bile acids (BAs) have crucial roles in modulating metabolic complications including obesity and diabetes. Our recent work suggested that BA overload in mice genetically deficient for the nuclear receptor FXR and SHP (double knockout, DKO) results in unexpected beneficial anti-obesity and anti-diabetes phenotype potentially through novel crosstalk between liver and adipose tissues. Preliminary analysis indicated that expression of the hepatokine orosomucoid 2 (ORM2) is dramatically increased by BA overload. Hepatic ORM2 overexpression improves glucose metabolism with dramatic reduction of adipose tissue weight in high fat diet-fed mice (HFD), proposing this little studied factor as a beneficial hepatokine in obesity and diabetes. We hypothesized that hepatokine ORM2 ameliorates obesity and diabetes through liver-adipose crosstalk. We propose two specific aims to delineate the molecular function of ORM2.
- We will investigate in vivo metabolic function of ORM2 in obesity and diabetes using Orm2 knockout (KO) mice.
- We will define molecular mechanism of ORM2 effect on adipose tissue through transcriptomic and proteomic profiling. This project will provide new and more detailed molecular mechanisms of liver-adipose tissue crosstalk, with potential to uncover therapeutic application of the new hepatokine ORM2 in obesity and diabetes.
Aaron Cox, Ph.D. - “Re-purposing anti-rheumatic drugs to treat obesity”
Obesity is associated with chronic low-grade inflammation, reflecting significant alterations in the composition of immune cell populations that reside in white adipose tissue (WAT). The ensuing pro-inflammatory environment likely impinges on the metabolic functions of adipocytes and may partially explain the insulin resistance that characterizes type 2 diabetes (T2D). We recently demonstrated ectopic expression of microRNA miR-30a in the subcutaneous fat pad of diabetic mice coupled improved insulin sensitivity and increased energy expenditure with decreased ectopic fat deposition in the liver and reduced WAT inflammation.
We subsequently pursued the notion that pharmacological inhibitors of inflammation that exhibit a gene expression profile similar to ectopic miR-30a expression in WAT should represent new drugs for insulin resistance and T2DM. To this end, we used the Broad Connectivity Map to analyze a library of small molecules that induce mRNA profiles similar to that of exogenous miR-30a expression in WAT. Through this process, we nominated the rheumatoid arthritis compound auranofin. Treatment of obese mice with auranofin improved insulin sensitivity and glucose tolerance. Auranofin treatment also normalized other obesity-associated abnormalities, including hepatic steatosis, serum insulin and leptin. Mechanistically, a combination of proteomics and immunophenotyping established auranofin likely exerts anti-diabetic activities by opposing low-grade inflammation in WAT and ectopic liver fat accumulation.
These studies reveal important metabolic properties of anti-inflammatory treatments that may be re-purposed as therapies for insulin resistance and T2DM.