# Control of brown adipocyte metabolism through a Kininogen-Bradykinin Receptor 2 Axis

> **NIH NIH F30** · UNIVERSITY OF PENNSYLVANIA · 2020 · $32,610

## Abstract

Project Summary/Abstract (limit 30 lines):
This application is for a fellowship awarded by the National Institute of Diabetes, Digestive and Kidney
Diseases to predoctoral physician-scientist trainees. This applicant is a trainee at the Medical Scientist Training
Program at the Perelman School of Medicine at the University of Pennsylvania. This award would provide him
with the opportunity to improve his research skills and scientific communication preparing him for a career as
an academic physician scientist studying diabetes and obesity pathogenesis. Obesity is a major driver of
mortality throughout the world. One approach for treating obesity is to target thermogenic adipose tissue, a
metabolic organ that burns energy to perform nonshivering thermogenesis. Harnessing thermogenic adipose
fat to increase energy expenditure has great therapeutic potential to treat obesity as increasing thermogenic
adipose function prevents diet-induced obesity in a variety of animal models. I have identified Kininogen 2
(KNG2) as a potential brown adipocyte-derived regulator of BAT metabolism. Kininogens are multifunctional
secreted proteins that produce the vasodilatory nonapeptide bradykinin (BK) upon enzymatic cleavage. BK
acts locally to activate its G-Protein Coupled Receptor, Bradykinin Receptor 2 (BDKRB2). I have determined
that Kininogen 2 mRNA is highly expressed in brown adipose tissue and regulated by a key lineage
determining factor, Early B Cell Factor 2. Furthermore, I have demonstrated that signaling through BDKRB2 is
required for basal and sympathetic-stimulated uncoupled respiration in brown adipocytes. Therefore, this
proposal will determine the mechanism by which a novel signaling axis through Kininogen 2 (KNG2) and
Bradykinin Receptor 2 (BDKRB2) regulates thermogenic adipose tissue acclimation using in vitro and in vivo
metabolic approaches. Understanding how brown fat facilitates acclimation to cold and harnessing brown fat
activity to increase energy expenditure have great therapeutic potential to treat obesity. These studies will
describe a role for a novel signaling axis in brown adipocyte metabolism with the ultimate goal of informing
obesity therapeutic generation.

## Key facts

- **NIH application ID:** 9857474
- **Project number:** 5F30DK120062-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Anthony Robert Angueira
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,610
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857474

## Citation

> US National Institutes of Health, RePORTER application 9857474, Control of brown adipocyte metabolism through a Kininogen-Bradykinin Receptor 2 Axis (5F30DK120062-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857474. Licensed CC0.

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