Nutrition and Metabolic Diseases
The Nutrition and Metabolic Diseases section is actively involved in clinical and basic research pertaining to the disorders of human nutrition and metabolism such as obesity, other body fat disorders, diabetes, and hyperlipidemias. Faculty are also involved in the training and teaching of students and postdoctoral fellows, and provide consultation to patients with lipid disorders, diabetes, and adipose tissue disorders.
Research studies pertain to inherited and acquired lipodystrophies, obesity, body composition, insulin resistance, management of diabetes mellitus, and hyperlipidemia.
We are investigating phenotypic characteristics, metabolic abnormalities, and underlying basis of various types of lipodystrophies and progeroid syndromes and other disorders of adipose tissues such as Multiple Symmetric Lipomatosis. Mutations of the AGPAT2 and BSCL2 genes in patients with congenital generalized lipodystrophy have been reported recently by our investigators. In addition, we have reported mutations in the Lamin A/C gene in familial partial lipodystrophy (Dunnigan variety) and in the PPAR gamma gene in a patient with familial partial lipodystrophy. Our laboratory discovered mutations in zinc metalloproteinase (ZMPSTE24) gene in patients with mandibuloacral dysplasia, type B. We have also reported a novel autoinflammatory syndrome of joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP). Subsequently, we identified PSMB8 gene mutation in patients with JMP syndrome. We have also reported remarkable success in the treatment of lipodystrophies using recombinant leptin therapy.
We are also involved in investigating the genetic basis of familial hypercholesterolemia and type 1 hyperlipoproteinemia (familial hyperchylomicronemias with deficiency of lipoprotein lipase deficiency or other associated proteins). We are conducting clinical trials to investigate novel therapies for patients with familial hypercholesterolemias and type 1 hyperlipoproteinemias.
Our previous studies highlight the importance of dietary fiber in the management of diabetes mellitus. We have also contributed significantly to the understanding of the drug treatment of diabetic dyslipidemia. Our studies have evaluated the efficacy and safety of nicotinic acid, lovastatin, gemfibrozil, and cholestyramine in treating lipid disorders in patients with diabetes
We provide clinical and research training to:
- Medical students and dietetic students
- Doris Duke clinical research fellows
- Postdoctoral research fellows
- Endocrinology, metabolism, and diabetes fellows
- Nutrition and metabolic diseases fellows
We manage patients with obesity, lipoprotein disorders, diabetes mellitus, and body fat disorders such as lipodystrophies. Faculty and clinical fellows provide consultation and services at the Internal Medicine Subspecialty Clinic at James W. Aston Ambulatory Center and at the Lipid Clinic at Parkland Memorial Hospital as well as the Department of Veterans Affairs Medical Center’s Diabetes and Lipid clinics. Patients with adipose tissue disorders are evaluated at the Center for Translational Medicine.
We are investigating the molecular mechanisms of lipodystrophies for both the genetic and acquired varieties. Opportunities are available to study the mechanisms by which recently identified gene defects cause lipodystrophies. These include creating knock-out and transgenic mice models, modification at the cellular levels and the biochemistry behind such defects. Because of the genetic heterogeneity of the lipodystrophies, identification of additional genes will become necessary using positional cloning approaches.
The lab is well equipped to carry out all such experiments, including cell culture experiments. The lab uses state-of-the-art core facilities at UT Southwestern for genetic analysis, molecular imaging, creating transgenic mice and phenotyping