G5 Doctoral dissertation (article)
Intramyocellular lipid metabolism in health, diet and exercise : a focus on lipid droplets and the perilipin protein family (2023)
Terveyden, ruokavalion ja liikunnan vaikutukset lihassolun lipidimetaboliaan : painopisteenä lipidipisarat ja perilipiiniproteiinit

Fachada, V. (2023). Intramyocellular lipid metabolism in health, diet and exercise : a focus on lipid droplets and the perilipin protein family [Doctoral dissertation]. University of Jyväskylä. JYU dissertations, 693. https://urn.fi/URN:ISBN:978-951-39-9733-5

JYU authors or editors

Publication details

All authors or editors: Fachada, Vasco

eISBN: 978-951-39-9733-5

Journal or series: JYU dissertations

eISSN: 2489-9003

Publication year: 2023

Number in series: 693

Number of pages in the book: 1 verkkoaineisto (89 sivua, 44 sivua useina numerointijaksoina,3 numeroimatonta sivua)

Publisher: University of Jyväskylä

Place of Publication: Jyväskylä

Publication country: Finland

Publication language: English

Persistent website address: https://urn.fi/URN:ISBN:978-951-39-9733-5

Publication open access: Openly available

Publication channel open access: Open Access channel

Abstract

This doctoral study investigated the role of perilipins (PLINs) in skeletal muscle lipid metabolism and their association with intramyocellular lipid droplets (LDs) in relation to health, exercise and and nutrition. Using diverse study models including human subjects, in vitro experiments, and advanced image analysis techniques, the study aimed to explore the effects of insulin resistance, physical activity, and branched-chain amino acid (BCAA) availability on PLIN coating of LDs and its implications for muscle phenotype. The results revealed that individuals with unhealthier skeletal muscle phenotypes exhibited deficient PLIN coating of LDs, particularly in the inner regions of glycolytic fibertypes. These findings were further validated in glycolytic myotubes subjected to BCAA deprivation, which also displayed reduced PLIN coating together with reduced LD turnover indicators. On the contrary, physical activity and balanced BCAA availability were associated with enhanced LD coating, which can provide protection against intramyocellular lipotoxicity. Moreover, the study uncovered the involvement of PLINs in various cellular processes within and between organelles, emphasizing the significance of their functional role beyond LD association. Notably, i t was observed that PLIN5 translocated to the nuclei following muscle contractions, suggesting its potential contribution to transcriptional pathways. In conclusion, this study highlights the crucial role of PLIN physiology in skeletal muscle lipid metabolism and overall muscle health. Appropriate physical activity and nutrition were found to positively impact muscle health by facilitating proper association of PLINs with intramyocellular LDs and engaging in diverse cellular functions. The study suggests that targeting the PLIN coating of LDs could hold therapeutic potential for metabolic diseases. Future research directions include further investigation of the different PLIN members, such as PLIN3 and PLIN4, and exploring the nature of a putative intramyocellular lipid network. Additionally, understanding the mechanisms underlying PLIN translocation to nuclei following muscle contractions opens up new avenues for studying the involvement of PLINs in transcriptional pathways related to energy metabolism.

Keywords: muscles; muscle cells; lipid metabolism; insulin resistance; lipids; amino acids; physical training; physical activity; dietetics; sports physiology; doctoral dissertations

Free keywords:  BCA A; PGC-1α; perilipins; insulin resistance; skeletal muscle; physical activity; lipotoxicity; lipid droplets; myotubes

Contributing organizations

Ministry reporting: Yes

VIRTA submission year: 2023