# Nuclear receptors and their Coactivators as Mediators of Systems Metabolism

> **NIH NIH P01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $1,505,750

## Abstract

Overall -­ Project Summary 
 
Obesity is approaching epidemic proportions as a nutritional and pathological disorder in the U.S. and is closely 
associated  with  important  syndromes  including  type  2  diabetes,  insulin  resistance,  hepatic  steatosis, 
dyslipidemias,  hypertension,  coronary  heart  disease,  osteoarthritis  and  cancer.  Obesity  rates  in  the  U.S.  have 
continued  to  worsen  whereby  nearly  70%  of  the  adult  population  is  overweight  and  the  yearly  medical  cost  of 
treatment  for  obesity-­related  disease  is  estimated  at  $190  billion,  currently  6X  the  annual  NIH  budget. 
Consequently,  obesity  is  anticipated  to  overtake  smoking  as  the  most  preventable  cause  of  adult  mortality. 
Therefore, public health initiatives focused on identifying therapeutic options to combat the detrimental effects of 
obesity-­related disease rely on an improved understanding of how alterations in metabolic tissue crosstalk alters 
metabolism  to  favor  energy  accretion  and  deposition.  Our  highly  synergistic  and  integrated  Program  Project 
team has identified previously unappreciated molecular mechanisms that highlight the coordinated actions of the 
hypothalamus (brain), liver and white adipose tissues as gatekeepers of metabolic energy balance that become 
dysregulated by overnutrition. By focusing on the metabolic actions of the Steroid Receptor Coactivator (SRC) 
family  as  amplifiers  of  nuclear  hormone  receptor  (NR)/transcription  factor  (TF)  function  in  this  triad  of  energy-­
responsive  tissues,  we  have  exposed  transcriptional  reprogramming  as  a  key  molecular  determinant  in  the 
disruption  of  normal  energy  homeostasis  arising  from  chronic  exposure  to  caloric  excess.  Such  a  complex 
metabolic regulatory axis, which involves the interplay of multiple tissue systems (i.e. brain, liver, adipose), and 
underlying transcriptional machinery (NR/SRCs) that maintain their homeostatic balance, can only be adequately 
studied by a multidisciplinary research team with unique, yet synergistic, expertise. Leveraging the collaborative 
framework of the NIDDK P01 Program Project, we have assembled such a team of scientists who are dedicated 
to the overall objective of understanding the ‘mechanisms’ for the downstream tissue-­specific metabolic functions 
of NR/SRC action that govern whole body energy balance.

## Key facts

- **NIH application ID:** 10153756
- **Project number:** 5P01DK113954-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** BERT W O'MALLEY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,505,750
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153756

## Citation

> US National Institutes of Health, RePORTER application 10153756, Nuclear receptors and their Coactivators as Mediators of Systems Metabolism (5P01DK113954-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153756. Licensed CC0.

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