scholarly journals Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Pablo Esteban Morales ◽  
Jose Luis Bucarey ◽  
Alejandra Espinosa
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Specific Cell ◽  
Muscle Lipid ◽  
Cell Compartments ◽  
Carbohydrate And Lipid Metabolism ◽  
Common Causes ◽  
Specific Lipid

Skeletal muscle is one of the main regulators of carbohydrate and lipid metabolism in our organism, and therefore, it is highly susceptible to changes in glucose and fatty acid (FA) availability. Skeletal muscle is an extremely complex tissue: its metabolic capacity depends on the type of fibers it is made up of and the level of stimulation it undergoes, such as acute or chronic contraction. Obesity is often associated with increased FA levels, which leads to the accumulation of toxic lipid intermediates, oxidative stress, and autophagy in skeletal fibers. This lipotoxicity is one of the most common causes of insulin resistance (IR). In this scenario, the “isolation” of certain lipids in specific cell compartments, through the action of the specific lipid droplet, perilipin (PLIN) family of proteins, is conceived as a lifeguard compensatory strategy. In this review, we summarize the cellular mechanism underlying lipid mobilization and metabolism inside skeletal muscle, focusing on the function of lipid droplets, the PLIN family of proteins, and how these entities are modified in exercise, obesity, and IR conditions.

193 Single Cell RNA-sequencing Reveals a Role of Lipid Metabolism in Muscle Satellite Cells

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 104-105
Author(s):  
Shihuan Kuang ◽  
Feng Yue ◽  
Stephanie Oprescu
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Cell Fate ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Lipid Droplets ◽  
Self Renewal ◽  
Droplet Dynamics ◽  
Single Cell Rna Sequencing

Abstract Single Cell RNA-sequencing (scRNA-seq) is a powerful technique to deconvolute gene expression of various subset of cells intermingled within a complex tissue, such as the skeletal muscle. We first used scRNA-seq to understand dynamics of cell populations and their gene expression during muscle regeneration in murine limb muscles. This leads to the identification of a subset of satellite cells (the resident stem cells of skeletal muscles) with immune gene signatures in regenerating muscles. Next, we used scRNA-seq to examine gene expression dynamics of satellite cells at various status: quiescence, activation, proliferation, differentiation and self-renewal. This analysis uncovers stage-dependent changes in expression of genes related to lipid metabolism. Further analyses lead to the discovery of previously unappreciated dynamics of lipid droplets in satellite cells; and demonstrate that the abundance of the lipid droplets in newly divided satellite daughter cells is linked to cell fate segregation into differentiation versus self-renewal. Perturbation of lipid droplet dynamics through blocking lipolysis disrupts cell fate homeostasis and impairs muscle regeneration. Finally, we show that lipid metabolism regulates the function of satellite cells through two mechanisms. On one hand, lipid metabolism functions as an energy source through fatty acid oxidation (FAO), and blockage of FAO reduces energy production that is critical for satellite cell function. On the other hand, lipid metabolism generates bioactive molecules that influence signaling transduction and gene expression. In this scenario, lipid metabolism and FAO regulate the intracellular levels of acetyl-coA and selective acetylation of PAX7, a pivotal transcriptional factor underlying function of satellite cells. These results together reveal for the first time a critical role of lipid metabolism and lipid droplet dynamics in muscle satellite cell fate determination and regenerative function; and underscore a potential role of dietary fatty acids in satellite cell-dependent muscle development, growth and regeneration.

Responses of skeletal muscle lipid metabolism in rat gastrocnemius to hypothyroidism and iodothyronine administration: a putative role for FAT/CD36

2012 ◽  
Vol 303 (10) ◽  
pp. E1222-E1233 ◽  
Author(s):  
Assunta Lombardi ◽  
Rita De Matteis ◽  
Maria Moreno ◽  
Laura Napolitano ◽  
Rosa Anna Busiello ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Protein Level ◽  
Oxidation Rate ◽  
Mitochondrial Protein ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Muscle Lipid ◽  
Mitochondrial Fatty Acid ◽  
Skeletal Muscle Lipid

Iodothyronines such as triiodothyronine (T3) and 3,5-diiodothyronine (T2) influence energy expenditure and lipid metabolism. Skeletal muscle contributes significantly to energy homeostasis, and the above iodothyronines are known to act on this tissue. However, little is known about the cellular/molecular events underlying the effects of T3 and T2 on skeletal muscle lipid handling. Since FAT/CD36 is involved in the utilization of free fatty acids by skeletal muscle, specifically in their import into that tissue and presumably their oxidation at the mitochondrial level, we hypothesized that related changes in lipid handling and in FAT/CD36 expression and subcellular redistribution would occur due to hypothyroidism and to T3 or T2 administration to hypothyroid rats. In gastrocnemius muscles isolated from hypothyroid rats, FAT/CD36 was upregulated (mRNA levels and total tissue, sarcolemmal, and mitochondrial protein levels). Administration of either T3 or T2 to hypothyroid rats resulted in 1) little or no change in FAT/CD36 mRNA level, 2) a decreased total FAT/CD36 protein level, and 3) further increases in FAT/CD36 protein level in sarcolemma and mitochondria. Thus, the main effect of each iodothyronine seemed to be exerted at the level of FAT/CD36 cellular distribution. The effect of further increases in FAT/CD36 protein level in sarcolemma and mitochondria was already evident at 1 h after iodothyronine administration. Each iodothyronine increased the mitochondrial fatty acid oxidation rate. However, the mechanisms underlying their rapid effects seem to differ; T2 and T3 each induce FAT/CD36 translocation to mitochondria, but only T2 induces increases in carnitine palmitoyl transferase system activity and in the mitochondrial substrate oxidation rate.

scholarly journals Effects of epinephrine on lipid metabolism in resting skeletal muscle

1998 ◽  
Vol 275 (2) ◽  
pp. E300-E309 ◽  
Author(s):  
Sandra J. Peters ◽  
David J. Dyck ◽  
Arend Bonen ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Lipid Synthesis ◽  
Hormone Sensitive Lipase ◽  
Simultaneous Estimation ◽  
Lipid Hydrolysis ◽  
Muscle Lipid ◽  
Triacylglycerol Hydrolysis ◽  
Skeletal Muscle Lipid ◽  
Glycogen Breakdown

The effects of physiological (0, 0.1, 2.5, and 10 nM) and pharmacological (200 nM) epinephrine concentrations on resting skeletal muscle lipid metabolism were investigated with the use of incubated rat epitrochlearis (EPT), flexor digitorum brevis (FDB), and soleus (SOL) muscles. Muscles were chosen to reflect a range of oxidative capacities: SOL > EPT > FDB. The muscles were pulsed with [1-14C]palmitate and chased with [9,10-3H]palmitate. Incorporation and loss of the labeled palmitate from the triacylglycerol pool (as well as mono- and diacylglycerol, phospholipid, and fatty acid pools) permitted the simultaneous estimation of lipid hydrolysis and synthesis. Endogenous and exogenous fat oxidation was quantified by14CO2and3H2O production, respectively. Triacylglycerol breakdown was elevated above control at all epinephrine concentrations in the oxidative SOL muscle, at 2.5 and 200 nM (at 10 nM, P= 0.066) in the FDB, and only at 200 nM epinephrine in the EPT. Epinephrine stimulated glycogen breakdown in the EPT at all concentrations but only at 10 and 200 nM in the FDB and had no effect in the SOL. We further characterized muscle lipid hydrolysis potential and measured total hormone-sensitive lipase content by Western blotting (SOL > FDB > EPT). This study demonstrated that physiological levels of epinephrine cause measurable increases in triacylglycerol hydrolysis at rest in oxidative but not in glycolytic muscle, with no change in the rate of lipid synthesis or oxidation. Furthermore, epinephrine caused differential stimulation of carbohydrate and fat metabolism in glycolytic vs. oxidative muscle. Epinephrine preferentially stimulated glycogen breakdown over triacylglycerol hydrolysis in the glycolytic EPT muscle. Conversely, in the oxidative SOL muscle, epinephrine caused an increase in endogenous lipid hydrolysis over glycogen breakdown.

The modified mitochondrial outer membrane carrier MTCH2 links mitochondrial fusion to lipogenesis

2021 ◽  
Vol 220 (11) ◽  
Author(s):  
Katherine Labbé ◽  
Shona Mookerjee ◽  
Maxence Le Vasseur ◽  
Eddy Gibbs ◽  
Chad Lerner ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fusion ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Carrier ◽  
Cellular Survival ◽  
Mitochondrial Elongation ◽  
Specific Lipid

Mitochondrial function is integrated with cellular status through the regulation of opposing mitochondrial fusion and division events. Here we uncover a link between mitochondrial dynamics and lipid metabolism by examining the cellular role of mitochondrial carrier homologue 2 (MTCH2). MTCH2 is a modified outer mitochondrial membrane carrier protein implicated in intrinsic cell death and in the in vivo regulation of fatty acid metabolism. Our data indicate that MTCH2 is a selective effector of starvation-induced mitochondrial hyperfusion, a cytoprotective response to nutrient deprivation. We find that MTCH2 stimulates mitochondrial fusion in a manner dependent on the bioactive lipogenesis intermediate lysophosphatidic acid. We propose that MTCH2 monitors flux through the lipogenesis pathway and transmits this information to the mitochondrial fusion machinery to promote mitochondrial elongation, enhanced energy production, and cellular survival under homeostatic and starvation conditions. These findings will help resolve the roles of MTCH2 and mitochondria in tissue-specific lipid metabolism in animals.

scholarly journals Exon 9-deleted CETP inhibits full length-CETP synthesis and promotes cellular triglyceride storage

2020 ◽  
Vol 61 (3) ◽  
pp. 422-431 ◽  
Author(s):  
Lahoucine Izem ◽  
Yan Liu ◽  
Richard E. Morton
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Full Length ◽  
Intracellular Lipid ◽  
Transfer Protein ◽  
Lipid Phenotype ◽  
Exon 9 ◽  
And Storage

Cholesteryl ester transfer protein (CETP) exists as full-length (FL) and exon 9 (E9)-deleted isoforms. The function of E9-deleted CETP is poorly understood. Here, we investigated the role of E9-deleted CETP in regulating the secretion of FL-CETP by cells and explored its possible role in intracellular lipid metabolism. CETP overexpression in cells that naturally express CETP confirmed that E9-deleted CETP is not secreted, and showed that cellular FL- and E9-deleted CETP form an isolatable complex. Coexpression of CETP isoforms lowered cellular levels of both proteins and impaired FL-CETP secretion. These effects were due to reduced synthesis of both isoforms; however, the predominate consequence of FL- and E9-deleted CETP coexpression is impaired FL-CETP synthesis. We reported previously that reducing both CETP isoforms or overexpressing FL-CETP impairs cellular triglyceride (TG) storage. To investigate this further, E9-deleted CETP was expressed in SW872 cells that naturally synthesize CETP and in mouse 3T3-L1 cells that do not. E9-deleted CETP overexpression stimulated SW872 triglyceride synthesis and increased stored TG 2-fold. Expression of E9-deleted CETP in mouse 3T3-L1 cells produced a similar lipid phenotype. In vitro, FL-CETP promotes the transfer of TG from ER-enriched membranes to lipid droplets. E9-deleted CETP also promoted this transfer, although less effectively, and it inhibited the transfer driven by FL-CETP. We conclude that FL- and E9-deleted CETP isoforms interact to mutually decrease their intracellular levels and impair FL-CETP secretion by reducing CETP biosynthesis. E9-deleted CETP, like FL-CETP, alters cellular TG metabolism and storage but in a contrary manner.

scholarly journals Role of proton MR for the study of muscle lipid metabolism

2006 ◽  
Vol 19 (7) ◽  
pp. 968-988 ◽  
Author(s):  
Chris Boesch ◽  
Juergen Machann ◽  
Peter Vermathen ◽  
Fritz Schick
Keyword(s):  
Lipid Metabolism ◽  
Muscle Lipid

scholarly journals Acylated Ghrelin and The Regulation of Lipid Metabolism in The Intestine

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
N. Auclair ◽  
N. Patey ◽  
L. Melbouci ◽  
Y. Ou ◽  
L. Magri-Tomaz ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Physiological Saline ◽  
Fatty Acid Uptake ◽  
Intimate Relationship ◽  
Acid Uptake ◽  
Acylated Ghrelin ◽  
Adipose Tissues ◽  
Syrian Golden Hamsters

AbstractAcylated ghrelin (AG) is a gastrointestinal (GI) peptide mainly secreted by the stomach that promotes cytosolic lipid droplets (CLD) hypertrophy in adipose tissues and liver. However, the role of AG in the regulation of lipid metabolism in the intestine remains unexplored. This study aimed at determining whether AG influences CLD production and chylomicron (CM) secretion in the intestine. The effects of AG and oleic acid on CLD accumulation and CM secretion were first investigated in cultured Caco-2/15 enterocytes. Intestinal lipid metabolism was also studied in Syrian Golden Hamsters submitted to conventional (CD) or Western (WD) diets for 8 weeks and continuously administered with AG or physiological saline for the ultimate 2 weeks. In cultured Caco-2/15 enterocytes, CLD accumulation influenced CM secretion while AG reduced fatty acid uptake. In WD hamsters, continuous AG treatment amplified chylomicron output while reducing postprandial CLD accumulation in the intestine. The present study supports the intimate relationship between CLD accumulation and CM secretion in the intestine and it underlines the importance of further characterizing the mechanisms through which AG exerts its effects on lipid metabolism in the intestine.

Development of leptin resistance in rat soleus muscle in response to high-fat diets

2000 ◽  
Vol 279 (6) ◽  
pp. E1374-E1382 ◽  
Author(s):  
Greg R. Steinberg ◽  
David J. Dyck
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Soleus Muscle ◽  
Leptin Resistance ◽  
Safflower Oil ◽  
High Fat ◽  
Muscle Lipid ◽  
High Fat Diets ◽  
Rat Soleus Muscle ◽  
Fat Diets

Direct evidence for leptin resistance in peripheral tissues such as skeletal muscle does not exist. Therefore, we investigated the effects of different high-fat diets on lipid metabolism in isolated rat soleus muscle and specifically explored whether leptin's stimulatory effects on muscle lipid metabolism would be reduced after exposure to high-fat diets. Control (Cont, 12% kcal fat) and high-fat [60% kcal safflower oil (n-6) (HF-Saff); 48% kcal safflower oil plus 12% fish oil (n-3)] diets were fed to rats for 4 wk. After the dietary treatments, muscle lipid turnover and oxidation in the presence and absence of leptin was measured using pulse-chase procedures in incubated resting soleus muscle. In the absence of leptin, phospholipid, diacylglycerol, and triacylglycerol (TG) turnover were unaffected by the high-fat diets, but exogenous palmitate oxidation was significantly increased in the HF-Saff group. In Cont rats, leptin increased exogenous palmitate oxidation (21.4 ± 5.7 vs. 11.9 ± 1.61 nmol/g, P = 0.019) and TG breakdown (39.8 ± 5.6 vs. 27.0 ± 5.2 nmol/g, P = 0.043) and decreased TG esterification (132.5 ± 14.6 vs. 177.7 ± 29.6 nmol/g, P = 0.043). However, in both high-fat groups, the stimulatory effect of leptin on muscle lipid oxidation and hydrolysis was eliminated. Partial substitution of fish oil resulted only in the restoration of leptin's inhibition of TG esterification. Thus we hypothesize that, during the development of obesity, skeletal muscle becomes resistant to the effects of leptin, resulting in the accumulation of intramuscular TG. This may be an important initiating step in the development of insulin resistance common in obesity.

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