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.
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.
The group currently offers three projects for prospective Master Students:
|Ashcroft, Stephen Paul||Postdoc||Zierath Group, Circadian Biology||+4535334677|
|Chubanava, Sabina||Research Assistant||Treebak Group, Molecular Metabolism||+4535332352|
|Dalbram, Emilie||PhD Student||Treebak Group, Molecular Metabolism||+4535333791|
|Dall, Morten||Postdoc||Treebak Group, Molecular Metabolism||+4535337088|
|Damgaard, Mads Vargas||PhD Student||Treebak Group, Molecular Metabolism||+4535326585|
|Ehrlich, Amy Melissa||Postdoc||Zierath Group, Circadian Biology||+4535332397|
|Hassing, Anna Skab||PhD Student||Treebak Group, Molecular Metabolism||+4535337702|
|Peluso, Augusto||Postdoc||Treebak Group, Molecular Metabolism|
|Treebak, Jonas Thue||Associate Professor||Group Leader, Treebak Group, Molecular Metabolism||+4524805398|
From the left: Emilie Dalbram, Anna Skab Hassing, Thomas Svava Nielsen, Mads Thue Damgaard, Astrid Linde Basse, Marianne Møller Andersen, Antonio Augusto, Bastos Peluso,Morten Dall, Sabina Chubanava and Jonas Thue Treebak.