Perilipin 5 fine-tunes lipid oxidation to metabolic demand and protects against lipotoxicity in skeletal muscle

Laurens, Claire; Bourlier, Virginie; Mairal, Aline; Louche, Katie; Badin, Pierre-Marie; Mouisel, Etienne; Montagner, Alexandra; Marette, André; Tremblay, Angelo; Weisnagel, John; Guillou, Hervé; Langin, Dominique; Joanisse, Denis R.; Moro, Cédric

doi:10.1038/srep38310

Cited by 71 publications

(70 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PLIN1 protein levels are decreased in the WAT of mice on a HFD in comparison with that of animals on a normal chow diet . In skeletal muscle, two independent studies found that PLIN5 protein expression is increased in mice upon exposure to a HFD . These findings are in agreement with a study performed in human muscle biopsies, in which PLIN5 protein levels were higher in obese and diabetic patients compared to those of healthy subjects .…”

Section: Contacts Between Mitochondria and Other Organellessupporting

confidence: 86%

“…Moreover, when mice overexpressing Plin5 are subjected to a HFD, they show upregulation of browning markers (Ucp1, Cidea, Adiponectin, Cebpa) in WAT, in comparison with wild-type mice. In line with these results, another study found that overexpression of PLIN5 reduces lipolysis and fatty acid oxidation and increases glycogen synthesis and glucose oxidation in human primary myotubes [220]. Nevertheless, augmented energy demand by forskolin application increases lipid oxidation in conditions of PLIN5 overexpression to a higher rate than in control myotubes.…”

Section: Metabolic Impact Of Alterations In Proteins Participating Inmentioning

confidence: 61%

See 1 more Smart Citation

Metabolic implications of organelle–mitochondria communication

2019

View full text Add to dashboard Cite

Cellular organelles are not static but show dynamism—a property that is likely relevant for their function. In addition, they interact with other organelles in a highly dynamic manner. In this review, we analyze the proteins involved in the interaction between mitochondria and other cellular organelles, especially the endoplasmic reticulum, lipid droplets, and lysosomes. Recent results indicate that, on one hand, metabolic alterations perturb the interaction between mitochondria and other organelles, and, on the other hand, that deficiency in proteins involved in the tethering between mitochondria and the ER or in specific functions of the interaction leads to metabolic alterations in a variety of tissues. The interaction between organelles is an emerging field that will permit to identify key proteins, to delineate novel modulation pathways, and to elucidate their implications in human disease.

show abstract

Section: Contacts Between Mitochondria and Other Organellessupporting

confidence: 86%

Section: Metabolic Impact Of Alterations In Proteins Participating Inmentioning

confidence: 61%

Metabolic implications of organelle–mitochondria communication

2019

View full text Add to dashboard Cite

show abstract

“…SFN treatment did not bring about any reduction of PLIN3 induced by FA but this may be because PLIN3 is expressed mainly at the beginning of LDs maturation, at which stage PLIN3 is playing a big role in protecting LDs against lipolysis. PLIN2 is a major component of LDs in hepatocytes and PLIN5 is primarily restricted to fatty acid oxidizing tissues . In this study, the most intense expressions of PLIN2 and PLIN5 were observed from days 6 to 10 of FA treatment in hepatocytes, at a stage which is important for the maturation of LDs due to their counteraction of lipolysis.…”

Section: Discussionsupporting

confidence: 48%

Targeting PLIN2/PLIN5‐PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets

Tian

Lei

Teng

et al. 2019

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope The effects of sulforaphane (SFN) on the maturation of lipid droplets (LDs)—the storage units for free fatty acids and sterols as triacylglycerides (TAG) and cholesterol esters (CE)—are far from being understood, despite the fact that SFN is known to be beneficial for ameliorating lipid metabolism disorders. Methods and Results High‐fat‐intake models are established in both HHL‐5 hepatocytes and rodents. The numbers and sizes of LDs are decreased by SFN. The accumulation of lipid core components (TAG & CE) is reduced and the expression of their key synthetases, acyl‐coenzyme A: diacylglycerol acyltransferases 2 (DGAT2) and acyl‐coenzyme A: cholesterol acyltransferases 1 (ACAT1), is also inhibited. Moreover, SFN decreases LD‐associated protein PLIN2 and PLIN5 expression, but not that of PLIN1 and PLIN3, both in vivo and in vitro. Furthermore, over‐expression of peroxisome proliferator‐activated receptor gamma (PPARγ) induces the accumulation of TAG and the up‐regulation of PLIN2 and PLIN5, which are not reversed by SFN. These results suggest that PPARγ may be a target of SFN in lipid metabolism. Conclusion SFN disturbs LD maturation by inhibiting the formation of the neutral lipid core and decreases PLIN2 and PLIN5 via down‐regulation of PPARγ.

show abstract

“…; Laurens et al . ). Not only is the expression of the PLIN proteins important, but also their distribution across LDs.…”

Section: Introductionmentioning

confidence: 97%

A 7‐day high‐fat, high‐calorie diet induces fibre‐specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle

Whytock¹,

Parry

Turner

et al. 2020

The Journal of Physiology

View full text Add to dashboard Cite

Key points We have recently shown that a high‐fat, high‐calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days’ HFHC diet on (1) skeletal muscle concentration of lipid metabolites, and (2) potential changes in the perilipin (PLIN) content of the lipid droplets storing intramuscular triglyceride (IMTG). The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to lipid droplet stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists in reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance. Abstract A high‐fat, high‐calorie (HFHC) diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LDs) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LDs has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (11 males, 2 females) healthy lean individuals (age: 23 ± 2.5 years; body mass index: 24.5 ± 2.4 kg m−2), following an overnight fast, before and after consuming a high‐fat (64% energy), high‐calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+101%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (+80%; P < 0.01), also in type I fibres only. We propose that these adaptations of LDs support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days’ HFHC diet.

show abstract

Perilipin 5 fine-tunes lipid oxidation to metabolic demand and protects against lipotoxicity in skeletal muscle

Cited by 71 publications

References 47 publications

Metabolic implications of organelle–mitochondria communication

Metabolic implications of organelle–mitochondria communication

Targeting PLIN2/PLIN5‐PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets

A 7‐day high‐fat, high‐calorie diet induces fibre‐specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle

Contact Info

Product

Resources

About