# O-GlcNAc modification in metabolic homeostasis

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $404,094

## Abstract

Obesity has become a global pandemic that poses massive economic and public health burdens worldwide. Adipose tissue has an enormous plasticity in response to nutrient availability. Nutrient flux into the hexosamine biosynthetic pathway leads to the posttranslational modification of nuclear, cytoplasmic, and mitochondrial proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) moieties. O-GlcNAc transferase (OGT) is responsible for the addition of GlcNAc moieties to target proteins. Our preliminary results show that deletion of OGT in mature adipocytes results in lipodystrophy and
transgenic overexpression of OGT promotes diet-induced obesity. Additionally, conditioned medium from OGT-deficient adipocytes modulates preadipocyte proliferation and differentiation in vitro. To illustrate how nutrient-sensing OGT impacts adipose tissue homeostasis, we hypothesize that OGT in mature adipocytes controls adipogenesis through paracrine regulation of preadipocyte proliferation and differentiation. Aim 1 will assess in vivo adipogenesis in adipose-specific OGT knockout and knockin mice. Aim 2 will determine the effects of adipose OGT on dietary regulation of adipogenesis and whole-body metabolism. Aim 3 will identify how OGT in mature adipocytes regulates preadipocyte proliferation and differentiation in a paracrine manner. Completion of the proposed studies will define adipocyte OGT as a nutrient sensor that mediates the paracrine regulation of adipogenesis and controls the development of obesity and co-morbidities.

## Key facts

- **NIH application ID:** 10017952
- **Project number:** 5R01DK089098-07
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Xiaoyong Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $404,094
- **Award type:** 5
- **Project period:** 2019-09-12 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017952

## Citation

> US National Institutes of Health, RePORTER application 10017952, O-GlcNAc modification in metabolic homeostasis (5R01DK089098-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017952. Licensed CC0.

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