The prevalence of obesity, a condition leading to several comorbidities including hypertension, dyslipidemias, coronary heart disease, stroke as well as several malignancies is on the rise in the US and worldwide leading to increasing morbidity and mortality. The mechanisms underlying the pathogenesis of obesity and associated conditions have not yet been elucidated and currently available therapeutic approaches are far from optimal. In the past few years, the scientific community realized that the adipose tissue is not an inert depot storage organ but an active endocrine organ secreting several hormones. We have thus been researching the biochemistry, physiology, pathophysiological importance and therapeutic significance of adipose tissue secreted hormones, i.e. adipokines, aiming at elucidating their function in humans. Although important and clinically useful new information has been accumulated and new compounds have been advanced to phase III clinical trials in humans (leptin, adiponectin inducing agents etc) several questions still remain. What is the role of novel adipokines? What physiological functions do they serve and how could we prove the concept of their clinical efficacy? How do they interact with other known hormones or novel, muscle secreted hormones, to alter energy homeostasis and metabolism? How could we exploit novel information to create clinical interventions to fight obesity and its complications? Addressing these and similar questions and training dedicated scientists, who by focusing on these questions will function as power multipliers, could lead to a substantial beneficial impact on clinical medicine and public health. Now an experienced mid-career clinical researcher, I have undertaken a series of patient-oriented research studies that contribute significantly towards addressing these important issues. This proposed K24 award will allow me and my mentees to continue focusing intensively on this area of research for the next five years, a critical period for the development of this field. Importantly, this K24 award will not only be expanding my potential for significant contributions in the field but will primarily be, by design of the K24 awards, the appropriate vehicle for nurturing the next generation of patient-oriented researchers in this field.
The specific aims of this proposal are: 1. To provide a nourishing professional environment for the training and advancement of the careers of beginning clinical researchers, who will be conducting studies within ongoing patient-oriented research projects in the area of physiology and therapeutic use of molecules important in the regulation of energy homeostasis, and 2. To supplement already funded research projects aiming at examining the role of adipokines, gastrointestinal tract secreted molecules and myokines in metabolic diseases including obesity, diabetes and associated comorbidities. As expected based on NIH guidelines, the work performed under this K24 grant will be building upon the infrastructure provided by prospective cohort studies, pharmacokinetic studies, ?proof of concept? clinical trials, and multicenter phase III-IV clinical trials already underway or planned.
Obesity is becoming a major public health care need, and obesity-related research is still expanding and growing. This proposed K24 award will allow me and my mentees to continue focusing intensively on the area of obesity and metabolism for the next five years, a critical period for the development of this field. Importantly, this K24 award will not only be expanding my potential for significant contributions in the field but will primarily be, by design of the K24 awards, the appropriate vehicle for nurturing the next generation of patient-oriented researchers in this field.
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|Farr, Olivia M; Mantzoros, Christos S (2018) Obese individuals with type 2 diabetes demonstrate decreased activation of the salience-related insula and increased activation of the emotion/salience-related amygdala to visual food cues compared to non-obese individuals with diabetes: A preliminary stu Diabetes Obes Metab 20:2500-2503|
|Perakakis, Nikolaos; Yazdani, Alireza; Karniadakis, George E et al. (2018) Omics, big data and machine learning as tools to propel understanding of biological mechanisms and to discover novel diagnostics and therapeutics. Metabolism 87:A1-A9|
|Farr, Olivia M; Tuccinardi, Dario; Upadhyay, Jagriti et al. (2018) Walnut consumption increases activation of the insula to highly desirable food cues: A randomized, double-blind, placebo-controlled, cross-over fMRI study. Diabetes Obes Metab 20:173-177|
|Perakakis, Nikolaos; Mougios, Vassilis; Fatouros, Ioannis et al. (2018) Physiology of Activins/Follistatins: Associations With Metabolic and Anthropometric Variables and Response to Exercise. J Clin Endocrinol Metab 103:3890-3899|
|Perakakis, Nikolaos; Upadhyay, Jagriti; Ghaly, Wael et al. (2018) Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function. Metabolism 85:240-249|
|Farr, Olivia M; Mantzoros, Christos S (2017) Treatment options to prevent diabetes in subjects with prediabetes: Efficacy, cost effectiveness and future outlook. Metabolism 70:192-195|
|Rifas-Shiman, Sheryl L; Fleisch, Abby; Hivert, Marie-France et al. (2017) First and second trimester gestational weight gains are most strongly associated with cord blood levels of hormones at delivery important for glycemic control and somatic growth. Metabolism 69:112-119|
|Farr, O M; Mantzoros, C S (2017) Obese individuals with more components of the metabolic syndrome and/or prediabetes demonstrate decreased activation of reward-related brain centers in response to food cues in both the fed and fasting states: a preliminary fMRI study. Int J Obes (Lond) 41:471-474|
|Perakakis, Nikolaos; Farr, Olivia M; Tuccinardi, Dario et al. (2017) Research advances in metabolism 2016. Metabolism 67:41-53|
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