# Adipose tissue metabolic changes in chronic kidney disease and its contribution to adiponectin resistance and post-transplant diabetes mellitus

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $390,000

## Abstract

Project Summary:
Post-transplant diabetes (PTDM), a common diagnosis following kidney transplantation, is strongly associated
with adverse outcomes and its pathophysiology is poorly understood. Adipose tissue produces multiple
cytokines or adipokines involved in inflammation and glucose metabolism. In patients with chronic kidney
disease (CKD), adipose tissue cytokine production is altered. We have shown that with loss of kidney function
there is increased production of both inflammatory cytokines and adiponectin in adipose tissue with concurrent
adiponectin resistance in peripheral muscle tissue. Our additional preliminary data indicate 1) TNFα levels are
associated with PTDM, 2) patients who develop PTDM have increased mRNA expression of TNFα and lower
adiponectin expression in visceral fat compared to those who do not develop PTDM, 3) in myoblast culture,
TNFα blunts adiponectin derived glucose transport. Our theory is that adiponectin resistance plays a key role
in impaired glucose uptake and insulin resistance in CKD. Moreover following kidney transplantation despite
improvement in kidney function, there will be a residual imbalance in adiponectin resistance and adiponectin
production among patients who develop PTDM. Our overall hypothesis for this study is that CKD
mediated adipose tissue inflammation and ROS contribute to development of PTDM by promoting
muscle and adipose tissue adiponectin resistance. Our study will investigate the role of inflammation and
ROS on adiponectin resistance and also the adipose and muscle tissue metabolic phenotype of patients that
develop PTDM in 2 aims: 1) To define mechanistic pathways by which uremia, inflammation and/or ROS
promote adiponectin resistance in muscle and adipose cells we will; i) expose myocytes and adipocytes to
uremia, inflammatory cytokines and ROS with and without adiponectin, ii) study adiponectin downstream
effectors and function (glucose transport and β-oxidation) following cytokine/uremia exposure, and iii)
determine if an antioxidant/anti-inflammatory treatment mitigates adiponectin resistance in muscle/adipose
cells exposed to cytokines/uremia. We will also conduct genetic modulation experiments by altering key
proteins from the inflammatory pathway and antioxidant regulators in order to determine if we can reverse the
metabolic phenotype induced by cytokine/uremia exposure; 2) To determine the phenotype of adipose and
muscle tissue in patients that develop PTDM, we will i) study macrophage infiltration, ROS, and ER stress in
adipose tissue of patients that develop PTDM compared to patients that do not, ii) study the metabolic profile of
adipose tissue from PTDM patients, and iii)study muscle mitochondrial function and adiponectin pathway in
patients that develop PTDM compared to patients that do not . This project will develop data to fill gaps in
knowledge on tissue metabolic changes in CKD that influence glucose regulation and on dysregulatory
mechanisms that contribute to PTDM...

## Key facts

- **NIH application ID:** 9935902
- **Project number:** 5R01DK111574-04
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Maria Paula Martinez Cantarin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2017-07-21 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935902

## Citation

> US National Institutes of Health, RePORTER application 9935902, Adipose tissue metabolic changes in chronic kidney disease and its contribution to adiponectin resistance and post-transplant diabetes mellitus (5R01DK111574-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9935902. Licensed CC0.

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