Skeletal muscle insulin resistance in prediabetes: a lipidomic perspective on diacylglycerols, ceramides, and phospholipids

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F25%3A00085948" target="_blank" >RIV/00023001:_____/25:00085948 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60460709:41210/25:102853 RIV/61989592:15110/25:73632754

Výsledek na webu

<a href="https://www.nature.com/articles/s41598-025-22745-1#Fun" target="_blank" >https://www.nature.com/articles/s41598-025-22745-1#Fun</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-025-22745-1" target="_blank" >10.1038/s41598-025-22745-1</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Skeletal muscle insulin resistance in prediabetes: a lipidomic perspective on diacylglycerols, ceramides, and phospholipids

Popis výsledku v původním jazyce

Lipid metabolism disorders, accompanied by the accumulation of lipids, are believed to contribute to skeletal muscle insulin resistance development. These alterations may attenuate insulin signaling and glucose uptake and utilization. However, the specific roles of individual lipids remain incompletely understood. The study examined the relationship between skeletal muscle lipid composition and insulin resistance in a non-obese prediabetic hereditary hypertriglyceridemic (HHTg) rats. Male HHTg rats aged 4 and 12 months, exhibiting insulin resistance, and dyslipidaemia were used in this study. Skeletal muscle lipidomic profiles were analyzed using tandem mass spectrometry. Compared to age-matched Wistar controls, HHTg rats exhibited increased serum triglycerides, elevated NEFA and impaired glucose tolerance. Impaired muscle insulin sensitivity in HHTg rats was associated with the accumulation of triglycerides and 1,3-diacylglycerols, and most notably with an increase in specific ceramide species (18:0, 22:0, 24:0, 24:1) in both 4- and 12-month-old animals. Elevated mRNA expression of Degs1, a key enzyme in ceramide biosynthesis, may underlie the observed ceramide accumulation. Lipidomic profiling revealed decreases in membrane phospholipids, including phosphatidylethanolamine (PE 41:2), lysophosphatidylcholine (LPC 22:6), and lysophosphatidylethanolamine (LPE 20:0). In HHTg prediabetic model, skeletal muscle insulin resistance develops independently of obesity and prior to diabetes onset, driven by the accumulation of lipotoxic diacylglycerols and ceramides, alongside a reduction in specific phospholipids and lysophospholipids. Impaired fatty acid oxidation and enhanced ceramide biosynthesis contribute to ectopic lipid deposition, with ceramides exerting a more pronounced effect on insulin signaling. Strain-specific alterations in lipid metabolism are more significant than age-related alterations.

Název v anglickém jazyce

Skeletal muscle insulin resistance in prediabetes: a lipidomic perspective on diacylglycerols, ceramides, and phospholipids

Popis výsledku anglicky

Lipid metabolism disorders, accompanied by the accumulation of lipids, are believed to contribute to skeletal muscle insulin resistance development. These alterations may attenuate insulin signaling and glucose uptake and utilization. However, the specific roles of individual lipids remain incompletely understood. The study examined the relationship between skeletal muscle lipid composition and insulin resistance in a non-obese prediabetic hereditary hypertriglyceridemic (HHTg) rats. Male HHTg rats aged 4 and 12 months, exhibiting insulin resistance, and dyslipidaemia were used in this study. Skeletal muscle lipidomic profiles were analyzed using tandem mass spectrometry. Compared to age-matched Wistar controls, HHTg rats exhibited increased serum triglycerides, elevated NEFA and impaired glucose tolerance. Impaired muscle insulin sensitivity in HHTg rats was associated with the accumulation of triglycerides and 1,3-diacylglycerols, and most notably with an increase in specific ceramide species (18:0, 22:0, 24:0, 24:1) in both 4- and 12-month-old animals. Elevated mRNA expression of Degs1, a key enzyme in ceramide biosynthesis, may underlie the observed ceramide accumulation. Lipidomic profiling revealed decreases in membrane phospholipids, including phosphatidylethanolamine (PE 41:2), lysophosphatidylcholine (LPC 22:6), and lysophosphatidylethanolamine (LPE 20:0). In HHTg prediabetic model, skeletal muscle insulin resistance develops independently of obesity and prior to diabetes onset, driven by the accumulation of lipotoxic diacylglycerols and ceramides, alongside a reduction in specific phospholipids and lysophospholipids. Impaired fatty acid oxidation and enhanced ceramide biosynthesis contribute to ectopic lipid deposition, with ceramides exerting a more pronounced effect on insulin signaling. Strain-specific alterations in lipid metabolism are more significant than age-related alterations.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10700 - Other natural sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific reports

ISSN

2045-2322

e-ISSN

2045-2322

Svazek periodika

15

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

"art. no. 38784"

Kód UT WoS článku

001609448500004

EID výsledku v databázi Scopus

2-s2.0-105020993046