# Asprosin, body weight, and risk of type 2 diabetes in U.S. men and women

> **NIH NIH R01** · BROWN UNIVERSITY · 2021 · $682,457

## Abstract

PROJECT SUMMARY
Asprosin, a newly identified glucogenic hormone through study of neonatal progeroid syndrome (NPS, or Marfan
lipodystrophy syndrome), may have both therapeutic and diagnostic implications for obesity and diabetes. The
gene encoding asprosin, FBN1, has unique extreme 3’ mutations resulting in hypoglycemic symptoms and low
plasma insulin levels in a few patients with the rare NPS. Considerable evidence has recently demonstrated
asprosin’s direct role in hepatic glucose production modulation, and asprosin immunologic neutralization in the
treatment of obesity and diabetes in mouse models. The direct effect of asprosin on type 2 diabetes (T2D)
incidence in humans has not been investigated in human populations. The current application aims to investigate
the potential causal role of asprosin for obesity and T2D development in two large and high-quality prospective
cohorts of men and women. We plan to integrate data on relevant genetic variations, biochemical markers, and
clinical phenotypes of obesity and T2D incidence in the national Women’s Health Initiative (WHI) and the men’s
Health Professionals Follow-Up Study (HPFS). Both WHI and HPFS are long-term prospective cohorts that have
been funded by the NIH with detailed and high-quality dietary, lifestyle, clinical, biochemical, and genomic data,
and a large number of well-characterized and validated incident T2D cases using standardized protocol
consistently over 20 years of follow-up. All incident T2D cases with existing genetic data and fasting blood
samples (n1=2,615) matched by an equal number of controls (n0=2,615) randomly selected from the same WHI
cohort of women, and 600 case-control pairs of men (n’=1,200) will be included using the identical nested case-
control design. Genotyping and validation analyses will be performed in an additional 1,076 T2D case-control
pairs (n”=2,152) without existing genetic data. Adopting both standard statistical methods and the cutting-edge
Mendelian randomization method for causal inference, we will leverage these exceptional resources and the
substantial investment of time and effort by WHI/HPFS study investigators over the past two decades to
investigate, in a most cost-efficient and timely manner, the effect of this novel and promising hormone – asprosin
– for obesity and T2D development. We will be the first to investigate 1) the distribution of plasma asprosin levels
in men and women, 2) the genetic variations affecting asprosin functions in diverse human populations, and 3)
the potential causal relation between asprosin and obesity and T2D in human populations of diverse ethnicity
including white or Caucasian American (CA), African American (AA), and Hispanic American (HA).

## Key facts

- **NIH application ID:** 10202592
- **Project number:** 5R01DK125403-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Atul Chopra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $682,457
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202592

## Citation

> US National Institutes of Health, RePORTER application 10202592, Asprosin, body weight, and risk of type 2 diabetes in U.S. men and women (5R01DK125403-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10202592. Licensed CC0.

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