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 and other peptides such as adiponectin, and incretins such as GLP-1 analogues in the treatment of obesity and the metabolic syndrome (insulin resistance, diabetes, hypertension, hyperlipidemia).
- Investigate the roles of leptin and neuropeptides in inflammation as well as the mechanisms underlying their roles.
- Investigate new molecular targets for the treatment of obesity, diabetes, and endocrine malignancies.
- Perform "proof of concept studies" involving leptin administration in humans to fully elucidate leptin's role in human physiology and disease.
Specific examples of ongoing research projects are outlined below.
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 leptin and 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 retain the beneficial effects of PPAR-γ activators but without side effects.
- Leptin and adipokine signaling in vitro and in vivo (rodents and humans).
- Irisin biology in humans.
We conduct large-scale epidemiologic investigations, including cross-sectional, case control, and cohort studies, to examine:
- Obesity associated malignancies.
- The role of adiponectin and other adipokines in predicting diabetes and its complications in humans, as well as the roles of adiponectin and the insulin-IGF-1 system in the pathogenesis of malignancies.
- Predictors of diabetes and cardiovascular disease in diabetic individuals 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.
- Psychosocial mediators of risk for diabetes and cardiovascular disease.
Our clinical research studies focus on:
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 levels, pulsatile secretion of leptin, 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 to 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
Randomized, double-blind, placebo-controlled trials investigating the effects of liraglutide (a GLP-1 analogue) in lean and obese diabetic subjects.
Nutrition studies including:
Short-term effects of walnut consumption in men and women with the metabolic syndrome through placebo-controlled, cross-over studies using changes in appetite and insulin resistance as our primary outcomes.
The effects of caffeinated coffee on body weight and glucose tolerance through small, but rigorous, placebo-controlled, short- and long-term interventional trials.
The effects of alcohol on adipokine levels and metabolic risk factors.
Controlled, randomized meal replacement weight loss studies designed to examine the effects of weight loss on insulin sensitivity and glucose regulation in overweight subjects.
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.