T32 Training Program in Metabolism, Endocrinology and Obesity

Fellow Profiles

Omar Mohtar

Predoctoral Fellow

MD/PhD candidate (Molecular and Translational Medicine)

Mentor: Kandror KV.

Description of the research project:

Leptin represents a central metabolic regulator that controls food intake, energy expenditure, neuroendocrine functions, carbohydrate and lipid metabolism, and several other important physiological functions of the mammalian organism. Production of leptin by adipocytes is controlled by nutrient uptake and/or energy status of the body, although the mechanism of this regulation is still unknown. Our preliminary data strongly suggest that the mTORC1-mediated signaling pathway regulates leptin expression at the level of transcription and translation thus coupling leptin production to nutrient uptake. Interestingly, the lipid droplet protein FSP27 (a.k.a. CIDEC) may also be involved in the regulation of leptin expression by mTORC1. This observation may help to explain why leptin expression is linked to the size of the adipocyte and total body fat. The molecular mechanisms of all these regulatory connections will be explored in vitro and in vivo using our newly created double transgenic mice that activate mTORC1 in response to doxycycline specifically in fat. Since the activity of mTORC1 can be regulated by nutritional signals in the meal, we expect to learn how to manipulate levels of circulating leptin and to adjust them to the needs of the body.

Courtney Rumala

Predoctoral Fellow

PhD candidate (Nutrition and Metabolism)

Mentor: Corkey BE.

Description of the research project:

It is well established that chronic excess glucose leads to impaired beta cell function. However, the mechanism(s) to how this may occur is not clear yet. This gap in knowledge has prompted us to define the signals and mechanisms that contribute to basal insulin hypersecretion induced by excess glucose, with a particular focus on 1) bioenergetic studies, 2) signaling of mammalian target of rapamycin complex 1 (TORC1), a nutrient sensitive kinase complex whose hyperactivation has been shown to promote hyperinsulinemia and 3) PIP4kγ, a substrate and regulator of TORC1.

Dylan Thomas

Postdoctoral Fellow

MD (Medicine)

Mentors: Corkey BE & Apovian C.

Description of the research project:

We are conducting a pilot clinical trial (NCT02783703) designed to assess the effects of medium chain triglycerides on insulin secretion dynamics and insulin sensitivity assessed by frequently sampled intravenous glucose tolerance testing. Our primary goal in this study is to show that consumption of medium chain triglycerides will decrease basal insulin secretion and hyperinsulinemia and will lead to improvement in the insulin sensitivity index. This may have important implications for the prevention of treatment of metabolic syndrome and type 2 diabetes and help elucidate the mechanisms underlying the racial disparities in diabetes outcomes. We are continuing to enroll patients and conduct study visits for this trial which is set to end in July 2018. In addition, I have performed an analysis on the effects of bariatric surgery on insulin sensitivity aliong with an analysis of whether there are differences in the risk of weight regain after bariatric surgery between racial groups which will be submitted for publication shortly.