Projects
Project Goals
The Mantzoros research group conducts independent investigations and collaborates on several projects with experts from national and international institutions. Our projects aim to:
- Investigate the etiology, underlying molecular mechanisms and pathophysiological links between obesity/adipose tissue diabetes, cardiovascular disease, and malignancies.
- Explore the role of promising new classes of anti-obesity medications including leptin or other peptides including melanocortin agonists, ghrelin, adiponectin, and ciliary neurotrophic factor in the treatment of obesity and the metabolic syndrome (insulin resistance, diabetes, hypertension, hyperlipidemia).
- Investigate the role of leptin and neuropeptides in inflammation as well as the mechanisms underlying this role of leptin.
- Investigate new molecular targets for the treatment of obesity and diabetes as well as endocrine malignancies.
- Investigate the role of adipokines in immune function, cardiovascular disease, and malignancies.
- Perform "proof of concept studies" in humans involving leptin administration to fully elucidate the role of leptin in humans.
Specific examples of ongoing research projects are outlined below.
Basic Research
The Mantzoros research group utilizes genomics-bioinformatics, molecular biology, and human investigation tools to discover and study novel molecules, especially adipokines, important in the pathogenesis of diabetes, obesity, and associated disease states, including cardiovascular disease and malignancies. Our animal physiology and molecular biology studies specifically examine:
- The role of hypothalamic neuropeptides and adipocyte secreted hormones in energy homeostasis/ obesity and insulin resistance/ diabetes.
- The role of new therapeutic agents important in the treatment of eating disorders and the metabolic syndrome.
- The role of adiponectin in the diagnosis and treatment of several obesity-related malignancies.
- In vitro investigations into the intracellular pathways that are activated by adiponectin as well as various in vivo models of colorectal cancer to help identify whether adiponectin plays a causal role in the development and progression of colorectal cancer.
- The biology of molecules upstream of adiponectin, such as PPAR-γ and PGC-1α. Our experiments examine the physiology and pathophysiology of PPAR-γ and PGC-1α in humans, as well as the potential therapeutic applications of selective PPAR-γ modulators, which will be retaining the beneficial effects of PPAR-γ activators but without side effects.
- Leptin and adipokine signaling in vitro and in vivo (rodents and humans).
Epidemiology
We conduct large-scale epidemiologic investigations, including cross-sectional, case control, and cohort studies on:
- The role of adiponectin and other adipokines in predicting diabetes and its complications in humans, as well as the role of adiponectin and the insulin, IGF-1 system in the pathogenesis of malignancies.
- Predictors of diabetes, as well as cardiovascular disease, in diabetics in the context of the Nurses Health Study and the Health Professionals Study.
- The Metabolic syndrome in HIV-positive patients.
- The etiology, clinical manifestations and response to bariatric surgery in obese patients.
Clinical Research
- The etiology and management of the metabolic syndrome in HIV-positive patients. Ongoing studies include interventional clinical trials that aim to test new treatment options for this syndrome, the efficacy and safety of a combination of leptin and pioglitazone as treatment for HAART-induced metabolic syndrome.
- The physiology of leptin in lean and obese individuals and the associations between leptin’s levels, pulsatile secretion, and neuroendocrine function to elucidate the role of leptin in mediating the neuroendocrine and immune response to starvation in humans.
- Randomized, double-blind, placebo-controlled trials investigate the effect of leptin treatment in:
- HIV positive subjects with the metabolic syndrome
- Obesity and the maintenance of reduced body weight
- Lean women with hypothalamic amenorrhea (HA) or polycystic ovary syndrome (PCOS)
- Bone density and bone metabolism in lean women with leptin deficiency
- Gonadal function, and other neuroendocrine axes of leptin deficient and leptin replete subjects
- The neurocircuitry associated with reward behavior downstream of, or independent from leptin, by using functional magnetic resonance imaging (fMRI)
- In vivo leptin signaling in adipose tissue and muscle
- Nutrition studies including:
- Short-term effects of walnut consumption in men and women with the metabolic syndrome, using changes in appetite and insulin resistance as our primary outcome of placebo-controlled, cross-over studies.
- The effects of caffeinated coffee on body weight and glucose tolerance through small, but rigorous, placebo-controlled, short- and long-term interventional trials.
- Randomized clinical trials in obese patients with diabetes including the Look AHEAD study, i.e., a study of health outcomes in response to weight-loss. In a national multi-center clinical trial, the Look AHEAD study, we examine the long-term effects of an intensive lifestyle intervention program designed to achieve and maintain weight loss by decreasing caloric intake and increasing physical activity, in overweight volunteers with type 2 diabetes.
- We are also conducting other interventional placebo-controlled trials for the treatment of diabetes and obesity.
