Molecular Metabolism in the Treebak Group

The overarching goal of the Treebak Group is to define the molecular and physiological mechanisms by which dietary compounds, weight loss, and physical activity improve metabolic health to prevent and treat obesity and type 2 diabetes.

Group photo of the Treebak Group
From left to right: Morten Dall, Jonas Thue Treebak, Augusto Peluso, Emilie Dalbram, Stephen Paul Ashcroft, Krzysztof Burek, Mads Vargas Damgaard, Amy Erlich, Thomas Lund, Sabina Chubanava, Anna Skab Hassing

 

 

 

We are defining mechanisms linking cellular nicotinamide adenine dinucleotide (NAD) to metabolic health. In particular, we aim to determine the role of the NAD+ generating and consuming pathways for maintaining tissue function and adaptability in response to metabolic stress. We employ innovative preclinical models to manipulate NAD-related metabolites cell type-specifically and determine functional implications. Moreover, we apply unbiased omics approaches and advanced analytical pipelines to identify responsible mediators and to determine genotype/phenotype interactions. Preclinical findings are tested and translated in clinical settings.

 

 

 

 

 

 

Nampt controls skeletal muscle development by maintaining Ca 2+ homeostasis and mitochondrial integrity
Published in Molecular Metabolism in 2021, this study determines the role of Nampt in skeletal muscle. We find that skeletal muscle-specific Nampt knockout mice have low NAD+ levels and exhibit a dystrophy-like phenotype that leads to juvenile death. This phenotype is linked to alterations in Ca2+ homeostasis and lack of NAMPT impairs mitochondrial function. Moreover, low NAD+ levels signals mitochondrial permeability transition pore (mPTP) opening, and in inhibition of the mPTP response using cyclosporin A improves sarcolemma integrity and increases survival rate. These findings highlight an important role of NAMPT for skeletal muscle metabolism and function.

“A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects”
Pre-clinical evidence suggests potent insulin sensitizing effects of dietary supplementation with the NAD+ precursor, nicotinamide riboside (NR). This study, published in American Journal of Clinical Nutrition in 2018, is the first to determine clinical potential of NR in middle-aged, obese and insulin resistant men. It finds no effects of NR on whole-body insulin sensitivity in the selected study group.

“Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity”
Published in Molecular Metabolism in 2018, this study characterizes the phenotype of mice with a skeletal muscle-specific knockout of the O-GlcNAc transferase (OGT). It shows that lack of OGT improves insulin sensitivity and enhances skeletal muscle glucose uptake. Moreover, OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating EZH2

“Mitochondrial function in liver cells is resistant to perturbations in NAD+ salvage capacity”
Published in Journal of Biological Chemistry in 2019, this study investigates the role of the enzyme nicotinamide phosphoribosyltransferase (NAMPT) in hepatocytes of mice. It shows that lack of Nampt does not affect mitochondrial respiratory capacity, possibly through enhanced flux through alternative NAD+ synthesis pathways.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Group Leader

Jonas T. Treebak
Associate Professor

Phone: +45 2480 5398
jttreebak@sund.ku.dk

Jonas Thue Treebak

Staff list

Name Title Phone E-mail
Ashcroft, Stephen Paul Postdoc +4535334677 E-mail
Burek, Krzysztof Laboratory Assistant   E-mail
Chubanava, Sabina Postdoc +4535332352 E-mail
Dalbram, Emilie PhD Student +4535333791 E-mail
Damgaard, Mads Vargas Research Assistant +4535326585 E-mail
Ehrlich, Amy Melissa Postdoc +4535332397 E-mail
Hassing, Anna Skab Research Assistant +4535337702 E-mail
Peluso, Augusto Postdoc   E-mail
Treebak, Jonas Thue Associate Professor +4524805398 E-mail
Yonamine, Caio Yogi Postdoc +4535327439 E-mail