Notice of Special Interest (NOSI): Advancing Research to Address the Heterogeneity of Obesity Risk, Related Health Outcomes, and Response to Treatment
Notice Number:

Key Dates

Release Date:

July 7, 2023

First Available Due Date:
October 05, 2023
Expiration Date:
September 08, 2027

Related Announcements

  • May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Required). See NOFO PA-20-183
  • May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185
  • April 16, 2019 - NHLBI Limitations on Clinical Trial Applications Submitted to the NIH Parent (R01 Clinical Trial Required) Funding Opportunity Announcement (FOA). See Notice NOT-HL-19-690. 

Issued by

National Heart, Lung, and Blood Institute (NHLBI)



This Notice of Special Interest (NOSI) aims to increase research to understand the heterogeneity of obesity phenotypes and the underlying mechanisms that protect against or increase risk for obesity and obesity-associated conditions. The objective of this NOSI is to support research applications that address knowledge and portfolio gaps regarding the role of obesity in disease development. Understanding the heterogeneity of obesity is necessary for precision and targeted implementation of obesity prevention and treatment interventions. Responsive proposals would include those aiming to investigate biological or nonbiological mechanisms through which adiposity differentially affects health. Other responsive applications might include those evaluating heterogeneity in response to obesity prevention and treatment, based on biological (e.g., genetic), behavioral, and/or racial/ethnic factors.


Obesity is a major contributor to cardiovascular disease (CVD) and other chronic diseases, and it has increased substantially in prevalence over the past 30 years in both the United States and globally. Efforts to combat the growing obesity epidemic, and its related health threats, require research that addresses the heterogeneity and complexity of obesity, including phenotypes, prevention, progression, and treatment. Heterogeneity can include both individual-level and population-level factors. For example, not all individuals with obesity are susceptible to adverse health problems typically associated with obesity. Various phenotypes of obesity, including metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), have been identified. MHO individuals have increased body fat but do not have the negative cardiometabolic health outcomes associated with the MUO phenotype. Similarly, individuals possessing a metabolically lean (ML) obesity phenotype have better health outcomes than those with a metabolically unhealthy lean (MUL) phenotype. Individuals also differ in terms of genetic and epigenetic susceptibility to obesity, propensity toward specific CVD subtypes, fat distribution, and behavior phenotypes. Before birth through early childhood, adolescence, and different stages of adulthood, a person's biology, behaviors, social situations, environments, and other factors evolve over time. Such factors may lead to individual-level obesity heterogeneity and may include demographics, psychosocial, socio-cultural, perceived discrimination and stigmatization. Research suggests that adipose tissue distribution patterns and function may better predict cardiometabolic disease risk in certain populations than current BMI cut points. Investigating the heterogeneity of obesity in diverse populations could lead to better understanding, prevention, and treatment of obesity-related health disparities.

Current “one-size-fits-most” approaches to prevention and treatment have arguably impeded efforts to alleviate the burden of obesity. Understanding factors of risk and resilience for obesity-related health conditions, as well as the mechanisms by which increased body fat or body fat distribution confers risk of disease to specific individuals or subgroups, can advance precision prevention and treatment strategies. In addition, understanding the trajectories of change in obesity phenotypes— for example, the transition of MHO to MUO can inform timing of precision interventions. Tackling obesity will require efforts that span the translational research spectrum, promote community-engagement, ensure health equity, and deploy cutting-edge technologies and approaches. The purpose of this NOSI is to stimulate research that would enable better understanding of the heterogeneity of obesity and the mechanisms underlying different obesity phenotypes. 

Responsive applications may include research that, 1) address differences in metabolic phenotypes of obesity (MUO, MHO, MUL, MHL), 2) address disparities in geographic regions with limited obesity research funding (IDeA states), and 3) supports and targets obesity research in racial/ethnic populations. As such, applications from investigators from IDeA-eligible states, minority-serving institutions (MSIs), and historically black colleges and universities (HBCUs) are especially encouraged.

Research topics within the scope of this NOSI may include, but are not limited to: 

  • Studies that use large scale epidemiologic data to understand the prevalence of different phenotypes of obesity/leanness (i.e., MHO, MUO, and ML, MUL) among diverse populations with a goal of developing universal definitions of adiposity 
  • Studies that identify heterogeneous populations with obesity (e.g., MHO, MUO, MUL, those with stigma) using multiple strategies (e.g., DEXA, polygenic risk scores) and intervene on such populations to prevent and treat obesity
  • Studies that examine heterogeneity of treatment response and maintenance of weight loss in current or previous obesity trials 
  • Research to understand the factors and behaviors underlying the heterogeneity in metabolic risk among people with similar BMI categories in diverse populations, including using longitudinal data, machine learning, and Artificial Intelligence methods 
  • Comprehensive approaches to assessing obesity, including genetics, -omics, environmental (e.g., geolocation technologies) and lifestyle factors to better diagnose individuals with obesity and provide the basis for targeted intervention, prevention, improved prediction, and prognosis 
  • Studies that examine predictors of healthy weight and weight-related behaviors and trajectories across the life course and across sex and race/ethnicity 
  • Heterogeneity of obesity associated risk for HLBS diseases and conditions (HF/COPD/OSA/Anemia) and co-morbidities 
  • Heterogeneity of maternal risk and adverse pregnancy outcomes among pregnant people with obesity 
  • Studies that examine how MHO transitions to MUO and the metabolic risk and CVD subtypes associated with the transition 
  • Studies that investigate the mechanistic effects of pharmacological interventions on adiponectin, leptin and other hormones in adipocyte metabolism 
  • Mechanistic studies that use ecological momentary assessment (EMA) tools to effectively identify predictors of health behaviors “in the moment” using machine learning techniques 
  • Studies on the implementation of evidence-based interventions and practices that target the predictors of healthy weight and weight-related behaviors in specific populations, especially those most impacted by health disparities 

Application and Submission Information

This notice applies to due dates on or after October 5, 2023 and subsequent receipt dates through September 7, 2027. No applications will be accepted on or after September 8, 2027.

Submit applications for this initiative using one of the following notices of funding opportunities (NOFOs) or any reissues of these announcements through the expiration date of this notice.

  • PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) 

Applicants who do not wish to use the target NOFOs listed above could consider submitting applications to NHLBI's suite of available Clinical Trial NOFOs located at:

NOTE: The NHLBI only permits mechanistic clinical trials via the Parent R01, Clinical Trial Required NOFO, PA-20-183, or its reissue. Efficacy CTs in response to this NOSI submitted to NHLBI via PA-20-183 or its reissue will be withdrawn. 

All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-HL-23-090 ”(without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Laurie Donze, PhD
National Heart Lung and Blood Institute (NHLBI)
Telephone: 301-827-1408

Candice Price, PhD
National Heart Lung and Blood Institute (NHLBI)
Telephone: 301-435-7764

Eric J Shiroma, ScD MEd
National Heart Lung and Blood Institute (NHLBI)
Telephone: 301-480-2695

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

John Diggs
National Heart Lung and Blood Institute (NHLBI)
Telephone: 301-827-8028