Scientific Programme
Physiology & Nutrition
IS-PN03 - Lipid droplets and mitochondria: The importance of a functional, dynamic relationship for metabolic health
Date: 03.07.2024, Time: 11:00 - 12:15, Lecture room: M1
Description
Historically, mitochondrial dysfunction has been linked lipotoxicity and the development of insulin resistance and type 2 diabetes (T2D). However, the link between mitochondrial dysfunction, lipid accumulation and insulin resistance are not straight-forward. In recent years, research has shown that lipid droplet (LD) morphology, fibre type and subcellular distribution, and the proteins coating LD, can mediate the relationship between muscle lipids and insulin resistance. Moreover, in healthy individuals the interaction between LD and the mitochondrial network is sensitive to nutrition and activity and demonstrates a remarkable flexibility where LD and mitochondria can adjust to changes in these factors. This raises the question as to whether mitochondrial function and/or dynamics are impaired in insulin resistance and T2D. This symposium will first present comprehensive evidence that questions the role of mitochondrial dysfunction in insulin resistance. Next, an overview of LD dynamics in response to acute and chronic exercise will be provided to lay the foundation for the final topic that will discuss the interaction between LD and the mitochondrial network. Therefore, in this symposium we will propose that LD and mitochondrial dynamics are key determinants of insulin resistance. By highlighting this topic, we hope to drive future research efforts aiming to develop therapeutic strategies to tackle the ongoing burden of T2D and obesity-related metabolic diseases.
Chair(s)
Jennifer Barrett
Liverpool John Moores University, Sport and Exercise Science
United Kingdom
David Morales-Álamo
Las Palmas University, Physical Education
Spain
Speaker A
Jennifer Barrett
Liverpool John Moores University, Research Institute for Sport & Exercise Science
United Kingdom
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Lipid droplet dynamics in health and disease
The aim of this talk is to present the current knowledge on how LD proteins respond to exercise training and their role(s) in regulating intramuscular triglyceride (IMTG) storage and utilisation during exercise. Our previous studies using immunofluorescence microscopy demonstrated that the expression of the LD-associated perilipin (PLIN) proteins are sensitive to a variety of exercise training types. Importantly, in healthy individuals at least, the expression of the PLIN proteins is closely aligned to IMTG content, and this relationship has implications for the regulation of the IMTG pool. In this context, this presentation will highlight the potential regulatory roles for the PLIN proteins in mediating IMTG storage and IMTG utilisation during exercise. This will include recent and new insights from studies employing time-course designs to reveal several important roles for the PLIN proteins contributing to the dynamic nature of LDs. Furthermore, these studies have also generated evidence that the PLIN proteins themselves are also dynamic, providing additional intrigue into the regulation of these proteins and directions for future work.
Speaker B
Katie Whytock
AdventHealth Orlando, Research Insitute of Sport and Exercise Science
United States
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Is skeletal muscle mitochondrial capacity impaired in individuals with insulin resistance and type 2 diabetes?
Impaired mitochondrial capacity has historically been linked to the development of insulin resistance (IR) in skeletal muscle (SkM); however this association remains controversial. Discrepancies in the literature may partially be attributed to the techniques employed to measure SkM mitochondrial capacities (enzymatic activities, ex vivo respiration, and in vivo ATP max/PCr recovery rates) and phenotypic differences [aerobic capacity, body mass index (BMI), and age] among the cohorts analyzed that are known to affect mitochondrial capacity. This talk will explore whether mitochondrial capacity is impaired in individuals with IR and T2D when confounding factors of age, BMI and aerobic capacity are accounted for and using an in-depth comprehensive suite of analyses including; in vivo PCr recovery, ex vivo mitochondrial respiration, supercomplex assembly, tricarboxylic acid (TCA) cycle intermediates, citrate synthase activity, transcriptomics and methylomics. Lastly, this talk will highlight the transcriptional and methylation profiles that underpin SkM IR that are not related to mitochondrial capacity and show whether these molecular profiles are retained in vitro in differentiated primary human skeletal muscle cells.
Speaker C
Anne Gemmink
Maastricht University, Nutrition and Movement Sciences
Netherlands
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The dynamic interaction between mitochondria and lipid droplets in health and disease.
Skeletal muscle represents a tissue with high plasticity, both structurally and metabolically. Muscle can readily adapt to fluctuations in energy demand and nutrient (substrate) availability. Thus, skeletal muscle (mal)adapts to longer periods of unloading and loading, but also to dynamically adapts to microcycles in energy demand and supply. Our lab is specifically interested into the dynamics in fuel storage and oxidation in skeletal muscle, the subcellular organelles involved and their spatial (re)orientation and interaction. Thus, we have studied dynamics in lipid droplet synthesis and degradation, mitochondrial network dynamics and interaction of lipid droplets with mitochondria and vice versa. We study these phenomena in humans over the entire range of energy expenditure, i.e. in obese sedentary individuals and in elite athletes. We also link this to read-outs of metabolic health and physical fitness. To this end, we use a variety of whole-body measurements of metabolic health and performance all the way down to super resolution microscopy to image and quantify dynamic processes of (a cluster of) molecules and organelles involved in lipid droplet en mitochondrial networks. Physical exercise and nutrient intake/deprivation are strong triggers to modulate lipid droplet and mitochondrial dynamics. In the presentation we will discuss how transient energy gaps, generated by exercise or short-term food deprivation, affect mitochondrial and lipid droplet interaction and if and how these dynamics are determinants of health and performance.