Exercise, metabolism and muscle in Xlab

Research focus

We focus on Human Integrative Physiology in Health and Disease. We make every effort to understand the metabolic and muscle remodelling behind exercise training, physical activity and diseases- from the whole body across organs, tissues, and cells to the intracellular environment.

We specifically study:

  • Metabolic, cardiovascular and muscle regulations 
  • The whole body: across regions and organs, tissue and cells
  • The morphology, integrity and function of organelles and muscle fibres
  • The molecular signalling pathways and metabolic processes
  • The intracellular compartmentalization as regulators of metabolic pathways
  • The proteins (expression, location, functionality and abundance) in a systems biology approach.

We use:

  • State of the art techniques in metabolic, muscle & cardiovascular research, as well as biochemical, immunochemical, biophysical and molecular biology analyses.

 We focus on:

  • Human physiology/pathophysiology and carry out advanced phenotyping in healthy subjects and patients, young and old
  • Developing new methods to use high resolution light microscopy as a research tool in human physiology.

We collaborate with:

  • Clinical research groups to study human liver, heart, skeletal muscle and/or visceral adipose tissue obtained in clinical trials
  • Research groups that utilize animal experimental models, including horses, pigs, rats and mice
  • Life Sciences industry.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Our research focuses on five main areas:

  • Training and physical activity
  • Mitochondrial physiology
  • Compartmentalized Metabolism
  • Muscle physiology
  • Physical activity and Health: Exercise is Medicine

Training and physical activity

This research area overall focuses on training, fat oxidation, metabolic fitness and biological age:

  • The effect of muscle lipids and particularly the bioactive lipid species diacylglycerol and ceramide influence on insulin sensitivity in humans.
  • The effect of training and physical activity/inactivity on fat metabolism, metabolic fitness and flexibility.
  • The mechanisms regulating muscle adaptation to training and/or inactivity and the effects of age and sex.
  • Lifestyle intervention and maintenance of positive lifestyle changes.
  • The effects of extreme long term endurance exercise in man and the influence of age.
  • The application and measurement biological age in the lab and in real world.

If you would like more information, please contact Jørn Wulff Helge, jhelge@sund.ku.dk.

Mitochondrial physiology

Within this research area, we perform high quality measures of the mitochondrial functionality. Our primary measures are respiratory analysis, measures of free radicals production and of the inner mitochondrial membrane potential. Furthermore, we measure several different mitochondrial related enzymes, proteins and gene expressions.

The lab holds equipment that enables us to investigate the mitochondrial function in several different types of tissues (skeletal, smooth and cardiac muscle, adipose and hepatic tissue).

We focus on regulatory mechanisms of oxygen transport and utilization in humans at rest and during exercise in health and in various pathological states, and the adaptations to exercise training, diet intervention and environment.

Equipment

  • Oroboros 2k, Innsbruck Austria (measures of oxygen consumption, membrane potential, ROS production)
  • Seahorse, Boston USA (measures of oxygen consumption and pH)
  • SAFAS, Monaco (flour spectrophotometer for measures of mitochondrial free radical production and mitochondrial membrane potential).

If you would like more information about the research or the equipment, please contact Steen Larsen stelar@sund.ku.dk.

Compartmentalized Metabolism

The focus of this research area is investigation of the role of intracellular compartmentalization of cellular processes on their regulation. We have described several novel regulatory mechanisms by which cells regulate metabolic pathways through the compartmentalization of substrates, enzymes and signaling molecules e.g.:

  • Gathering of glycogen related enzymes on a spherical structure formed in cells with critically low levels of glycogen to increase re-synthesis efficiency (Prats et al. 2006 and 2009),
  • Insulin stimulation signaling travels through the transverse tubuli membrane towards the inner regions of muscle fibers (Lauritzen et al. 2006)
  • Hormone Sensitive Lipase needs to translocate to the lipid droplets surface in order to utilize skeletal muscle triacylglycerides (Prats et al 2006).

Recently, using high resolution confocal microscopy, we have reported severe morphological alterations in the quality of skeletal muscle lipid droplets and mitochondrial networks in subjects with morbid obesity, alterations that are reversed with surgery-induced weight loss and linked to improvements in insulin sensitivity ( Kristensen et al 2018).

Research focus

  • Lipid droplets coating by PLINs and morphological integrity
  • Mitochondrial networks structural organization and dynamics. Link to organelle function
  • Glycogen storage quality and role of intracellular compartmentalization in the regulation of glycogen metabolism
  • Microscopy – super resolution structured illumination microscopy to investigate intracellular structure of compartments and their interaction
  • Carnitine transporter OCTN2, regulation by insulin and effects of severe mutations on whole body health

If you would like more information, please contact Clara Prats, cprats@sund.ku.dk.

Muscle physiology

Our research focuses on:

  • Understanding the molecular and cellular mechanisms causing acquired and genetic muscle disorders (eg congenital myopathies, muscular dystrophies, ageing syndromes)
  • Testing exercise as a countermeasure
  • Providing sufficient knowledge to identify drug targets and to design novel therapeutic interventions in preclinical animal models.

Our laboratory uses human and animal muscle samples, and techniques ranging from single-molecule biophysics to muscle cell physiology and from X-ray diffraction to high-resolution confocal/super-resolution microscopy

If you would like more information, please contact Julien Ochala, julien.ochala@sund.ku.dk

Physical activity and Health: Exercise is Medicine

In this line of research we study cardiovascular and metabolic adaptations to physical activity and inactivity, sport and physical training in healthy and diseased (e.g. type 2 diabetes, obesity, metabolic syndrome), young and old people.

We focus on cross-sectional and longitudinal human studies, using advanced physiological techniques, including methods for:

  • Blood and tissue (muscle and adipose tissue) sampling.
  • Body composition (weight, height, DXA scanning, Bio-impedance).
  • Cardio-respiratory fitness (V̇O2max).
  • Resting Metabolic Rate, substrate utilisation, maximal fat oxidation.
  • Muscle strength and power (handgrip dynamometer, Kin-Con (isometric-, isokinetic and-isotonic), Nottingham Power-rig).
  • Functional tests (6 min walk test, Chair-Stand-Test etc.).
  • Blood flow (strain gauge plethysmography, Ultrasound Doppler).
  • Arterio-venous catheterization (forearm, leg).
  • Eu-/iso- glycemic hyperinsulinemic clamp, hyperglycemic clamp, oral glucose or lipid tolerance test, meal test.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Ongoing research projects in Xlab

Myosin dysregulation in congenital myopathies

Responsible: Alexander Sonne, PhD student
Project dates: 10/2020 – 09/2023
Summary: Whatever the mutation is, the project aims to prove that myosin dysfunction is a key regulator and contributor of the muscle symptoms

Exploring dual-filament regulation in vertebrate muscle

Responsible: Elise Thomsen, PhD student
Project dates: 02/2021 – 01/2024
Summary: The project aims to identify how myosin and actin have diversified across the vertebrate kingdom and whether their function/metabolic demand have also adapted

Mechanisms underlying nemaline myopathy

Responsible: Jenni Laitila, postdoc
Project dates: 10/2020 – 03/2022 (or 03/2024)
Summary: The project aims to decipher how sarcomeric proteins have maladapted in the context of the most common non dystrophic genetic muscle disease, nemaline myopathy

Epigenetics landscape in congenital myopathies

Responsible: Rob Seaborne, postdoc
Project dates: 09/2021 – 08/2023
Summary: The project aims to define whether epigenetic remodeling worsens muscle symptoms and is a disease modifier

Myosin binding protein C regulation in health and disease

Responsible: Chris Lewis, postdoc
Project dates: 04/2021 – 03/2024
Summary: The project aims to characterize the post-translational modifications on myosin binding protein C, whether they modify myosin function in diabetes and whether this constitutes a good therapeutic target for obesity

Myosin function in hypertrophic cardiomyopathy

Responsible: Anna Kruselj, Erasmus student
Project dates: 09/2021 – 01/2022
Summary: The project aims to identify whether myosin maladaptation contributes to the phenotype of hypertrophic cardiomyopathy using mouse models

Genetic and epigenetics of Greenland shark muscle

Responsible: Marlene Musial, Erasmus student
Project dates: 10/2021 – 06/2022
Summary: The project aims to explore the specificity of Greenland sharks (who have a life expectancy of more than 200 years) genome and epigenome

Do mavacamten and physical activity have similar consequences on myosin function and subsequent muscle metabolism?

Responsible: Lee Tabrizian, Master Student
Project dates: 11/2021 – 06/2022
Summary: The project is focusing on physical activity as a potential regulator of myosin conformation and subsequent muscle metabolism. It also aims to prove that mavacamten mimics physical activity.

GLP1-Exisecret: Interaction of aerobic exercise and GLP-1 receptor agonist treatment on beta cell function in T2DM

Responsible: Arthur Ingersen, PhD student
Involved: Malte Schmücker, PhD student/stud.med. Peter Sørensen, Master Student
Project dates: 09/2019 – 11/2022
Summary: The effect of physical training on insulin secretory capacity in patients with type 2 diabetes with and without simultaneous GLP1-RA treatment. 

TRAINAiD: Training adaptations in type 2 diabetes

Responsible: Maria Hansen, PhD student
Involved: Ida Blom MA student, Kristine Kjær Lange MA student.
Project dates: 10/2020 – 10/2023
Summary: The mechanism behind the insulin sensitizing effect of physical training explored by single nuclei transcriptomics from skeletal muscle

IFAST: Metabolic effects of alternate day fasting in obese patients with and without type 2 diabetes.

Responsible: Arthur Ingersen, PhD student; Hildegunn Rømma Helset, Master Student; Monika Calov, Bachelor Student, Elizaveta Chabanova, chief physician; Eva Gjerlevsen Nielsen, Master Student, Christina Jensen, Master Student.
Project dates:  – finish 01/2022
Summary: The role of occilations in energy stores on insulin action in obese people with and without type 2 diabetes

STATIN-STOP: The effects of 2 months of discontinuation of statin treatment on muscle strength, functional capacity, and blood lipid concentrations in elderly people.

Responsible: Morten Bruun Korsholm, MD; Sofie Kirstine Strømgaard, MD; Thea Winther Pødenphanth, MD; Christina Alexandersen, MA Student, Ida Blom MA student.
Project dates:  01/2020 – 02/2022
Summary: Muscle mass and function do not change with discontinuation of statins. Mitochondrial respiratory capacity await analyses.

TAW: Maximal fat oxidation in young and old trained and untrained women

Responsible: Ronni Sahl, PhD student; Ida Marie Dahlgaard Hansen, Julie Wismann, Involved: Johanne Modvig, Alba Blasco Lorente
Project dates: 5/20 – 12/22
Summary: Effects of age, fitness and obesity on MFO and adipose tissue macrophage inflammation and mitochondrial function.

Beetox: The effects of beetroot juice supplementation on oxygen availability and efficiency at whole-body, muscle and mitochondrial level at rest and during exercise in type 2 diabetes and ageing.

Responsible: Arthur Ingersen, PhD student, Malte Schmücker, PhD student/stud.med.
Project dates: Hopefully finishing January 2022
Summary: Effects of beetroot juice on mitochondrial P/O ratio

Mitochondrial energy expenditure in obesity

Responsible: Jens Frey Halling, postdoc
Project dates: September 2021 – August 2023
Summary:  This project will investigate how energy expenditure is regulated by post-translational changes in the mitochondrial proteome of human subjects with/without obesity as well as in a pre-clinical mini-pig model, which shows an extraordinary downregulation of BMR upon energy restriction.

12 months of Endurance training – effect on mitochondria and blood volume

Responsible: Steen Larsen
Project dates: January 2021 - ??
Summary: Multiple biopsies will be obtained over the 12 month period. Focus will be mitochondrial respiratory capacity and content.

Amylin and calcitonin receptor agonist (KBP-066A) treatment – effect on mitochondria

Responsible: Steen Larsen
Involved: Matthias Flensted-Jensen, MA student
Project dates: August 2021 – July 2022
Summary: It has been reported that KBP-066A has an effect on body weight where a significant loss is seen after treatment. This weight loss is seen without a reduction in energy intake, indicating that metabolism is increased. Focus will be on mitochondrial function in adipose tissue, liver and muscle.

Aging, NASH and mitochondria (GUBRA)

Responsible: Steen Larsen; Mathias Flensted-Jensen, RA; Cecilie H. Andersen, Master Student
Project dates: Jan 2021-Jan 2022
Summary: Effect of aging and fatty liver on hepatic mitochondrial function

MetBC: The risk of metabolic diseases after chemotherapy in women with breast cancer

Responsible: Linn Gillberg, postdoc; Ida Bager Christensen, Master student; Agnes Lindholm, Master student
Project dates: Dec 2019 – Jan 2023
Summary: Women treated for breast cancer have an increased risk of developing type 2 diabetes. We investigate why this is the case by studying blood and tissue samples from breast cancer patients before their chemotherapy treatment and during 5 years thereafter.

iTAPH: Biological drug treatment of Psoriasis effect on inflammation

Responsible: Ronni Sahl, PhD student
Project dates: 6/2019 – 9/2022
Summary: The effect of biological treatment with anti-TNFalfa on adipose tissue inflammation in Psoriasis and Hidradenitis suppurativa patients.

CBMR project, EXPO (PI Christoffer Clemmensen)

Responsible: Ronni Sahl, PhD student
Project dates: 1/2019 - ?
Summary: The influence of overfeeding on appetite and metabolic regulation.

UBBERUP
  1. The factors that determine maintenance of lifestyle modifications and weight loss (WB-longitudinal).
    Responsible: Jørn W Helge; Steen Larsen
    In writing.
    Summary: Factors influencing lifestyle and weight maintenance in a one-year follow up.
  2. Lifestyle intervention; effects on systemic and AT-inflammation
    Responsible: Ronni Sahl, PhD student
    Project dates: -> 3/23
    Factors influencing lifestyle and weight maintenance in a one-year follow up.
  3. Bioage validation. Validating measurement of Biological age at Ubberup
    Responsible: Karina Husted, PhD student; Involved: Tue Rømer, RA; Mikkel Thunestvedt Hansen, PhD student; Mathilde Fogelholm, MsC
    Project dates: 1/2021 – 7/2022
    Summary: Proof of concept by measuring biological age before and after lifestyle intervention at Ubberup
HiLoMFO: Maximal fat oxidation and fuel use during exercise

Responsible: Sofie Vestergaard, PhD student; Emilie Ahmt Pedersen, Master Student; Eloise Tarry, MsC; Mike C. Olsen, MsC
Project dates: 10/20 – 12/22
Summary: The effect of fat or carbohydrate rich diet on MFO.

Ventriject: Validation of method to determine maximal oxygen uptake at rest using Ventriject equipment and validated towards direct measurement of VO2max.

Responsible: Mikkel Hansen, PhD student; Tue Rømer, RA
Involved: Amalie Højgaard, Stud med
Project dates: 1/2020 – 3/2022
Summary: Validation of Ventriject methodology.

Proposition of an index estimating biological age from physiological biomarkers of healthy aging

Responsible: Karina Husted, PhD student; Mathilde Fogelholm, MsC; Pernille Hulst, MsC; Jens Christian Brings Jacobsen, Assoc Prof., all BMI. Andreas Brink-Kjaer, PhD student; Kaj-Åge Henneberg, Assoc. Prof.; Helge Bjarup Dissing Sorensen, Assoc Prof., all DTU
Project dates: 1/2019 – 3/2022
Summary: Methodology study to establish a new algorithm to estimate biological age.

Variation of Biological age measurement

Responsible: Karina Husted, PhD student
Involved: Mikkel Thunestvedt Hansen, PhD student; Tue Rømer, RA; Amalie Højgaard, Stud med
Project dates: 1/2020 – 9/2022
Summary: Measuring the variation in biological age estimation.

Soccer project

Responsible: Tue Rømer, RA, Mikkel Hansen, PhD student
Involved: Kristine Lange, MA student; Anders Ibh, BA student; Mikkel L. Petersen, BA student
Project dates: 10/2020 – 3/2022
Summary: Validation of ventriject and effect of training and player position on MFO in Danish subelite players.

The effect of Glycogen stores on MFO

Responsible: Tue Rømer, RA
Project dates: 1/2022 – 12/2022
Summary: The influence of glycogen stores on MFO

Validation of Seismofit® to determine VO2max in patients with med heart failure or ischemic heart disease

Responsible: Mikkel T. Hansen, PhD student
Involved: Morten Kjøbek Lamberts, Emil Wolsk, Samuel Schmidt, Tor Biering Sørensen 
Project dates: 3/2021 – 6/2023
Summary: Three studies validating application of SeismoFit in heart patients.

Palermo
  1. Extreme exercise affects old and younger men differently
    Responsible: Jørn Helge; Jacob Frandsen, PhD student
    Involved: Ronni Eg Sahl, Tue Rømer, Mikkel Thunestvedt Hansen, Andreas Blaaholm Nielsen, Michelle Munk Lie-Olesen, Hanne Kruuse Rasmusen, Ditte Søgaard, Arthur Ingersen, Mads Rosenkilde, Steen Larsen, Flemming Dela
    Paper in review.
  2. Adipose tissue inflammation
    Responsible: Ronni Eg Sahl, PhD student
    Project dates: – 3/2023
    Summary: The effect of extreme exercise on systemic and adipose tissue inflammation
  3. Effect on heart function
    Responsible: Hanne Rasmusen
    Project dates: Old – 3/2023
    In writing.
  4. Effect on metabolomics, proteomics, myosin head status, microbiota
    Responsible: Jørn W. Helge
    Project dates: – 3/2023
    Summary: The effect of extreme exercise on metabolomics, proteomics, myosin head status, microbiota
CTD: Carnitine Transport Deficiency - Insulin effect, mito function and transport regulation

Responsible: Rannvá Dahl, PhD student
Project dates: January 2020 – May 2022
Summary: Investigate the effect of high insulin levels (clamp) on carnitine uptake in CTD patients.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Xlab is responsible for multiple events and courses. You can read about upcoming events and courses as well as past events and courses.

Upcoming Events and Courses

Currently no upcoming events

Past Events and Courses

  • Mitochondrial Physiology Summer School 2019 – From Organelle to Organism, 19-23 August
  • Mitochondrial Medicine Symposium, 9 March 2018
  • Cellular Bioenergetics Course 5-8 March 2018
  • Mitochondrial Physiology Summer School 2017
  • Mitochondrial Physiology Summer School 2015 - From Organelle to Organism
  • Mitochondrial Physiology Summer School 2013
  • Graduate Course 2010

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Alle studieretninger – emner egnet til både BA og MA specialer.

Vi beskæftiger os med fysisk aktivitet og inaktivitet indflydelse betydning for organismens funktioner. Nedenfor ses en liste af emner/stikord som du måske kan genkende dig selv i?

  • Kardiovaskulær, metabolisk og morfologisk adaptation til fysisk træning og inaktivitet
  • Fysisk træning i forebyggelsen og behandlingen af Type 2 diabetes
  • Insulin sekretion og insulin resistens
  • Mitokondrie fysiologi – hvordan omsættes næringsstofferne til energi?
  • Intramuskulært fedt hos atleter og insulin resistente personer. Hvordan hænger det sammen?
  • FatMax – evnen til af forbruge fedt som brændstof under fysisk aktivitet
  • Mitokondrielle netværk i muskler hos patienter med diabetes og/eller fedme. Belyst ved avanceret mikroskopi
  • Carnitine transport regulation by insulin
  • Fysisk træning af ældre mennesker mhp. at forebygge tab af muskelmasse- og styrke
  • Sarcopeni – betydning, forebyggelse og behandling
  • Body-Age – er det rent fup?
  • Livsstilsintervention - fastholdelse af gode livsstilsvaner

+ Mange andre muligheder, gerne tilpasset dine interesser inden for fysisk aktivitet og sundhed.

Er du interesseret, så skriv til:

Professor Flemming Dela,fdela@sund.ku.dk
Professor Jørn Wulff Helge,jhelge@sund.ku.dk
Lektor Steen Larsen,stelar@sund.ku.dk
Lektor Clara Prats,cprats@sund.ku.dk

Specifikke projekter:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Xlab secretary

Secretary
Jacqueline van Hall

Phone: +45 3532 7423
jacq@sund.ku.dk

Senior researchers in Xlab

Name Title Phone E-mail
Flemming Dela Professor +45 353-27425 Email
Jørn Wulff Helge Professor +45 287-57506 Email
Steen Larsen Associate professor +45 211-51924 Email
Julien Ochala Associate professor Email

Publications by Flemming Dela

Publications by Julien Ochala

Publications by Jørn Wulff Helge

Publications by Steen Larsen

Group members

Name Title Phone E-mail
Aske Wulff Helge Teaching Assistant   E-mail
Hanne K. Rasmusen Guest Researcher   E-mail
Jacqueline van Hall Research Group Secretary +4535327423 E-mail
Jeppe Bach Laboratory Technician. +4535327576 E-mail
Karina Louise Skov Husted Research Assistant +4528127945 E-mail
Kristine Kjær Lange Administrative Officer   E-mail
Linn Gillberg Postdoc   E-mail
Malte Schmücker PhD Student   E-mail
Maria Hansen PhD Student   E-mail
Mathias Flensted-Jensen Research Assistant +4535320326 E-mail
Rannvá Dahl PhD Student   E-mail
Robert Arthur Elliston Seaborne Postdoc   E-mail
Ronni Eg Sahl PhD Fellow   E-mail
Thomas Nyegaard Beck Laboratory Technician.   E-mail

Xlab is part of

Center for Healthy Aging

CopenAge

CAG for Physical activity and sport in clinical medicine

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