Contribution of glucose and glutamine to hypoxia-induced lipid synthesis decreases, while contribution of acetate increases, during 3T3-L1 differentiation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43927736" target="_blank" >RIV/00064173:_____/24:43927736 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10487590 RIV/00216208:11120/24:43927736 RIV/00216208:11310/24:10487590 RIV/00064190:_____/24:10001288 RIV/00064165:_____/24:10487590

Výsledek na webu

<a href="https://doi.org/10.1038/s41598-024-79458-0" target="_blank" >https://doi.org/10.1038/s41598-024-79458-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-024-79458-0" target="_blank" >10.1038/s41598-024-79458-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Contribution of glucose and glutamine to hypoxia-induced lipid synthesis decreases, while contribution of acetate increases, during 3T3-L1 differentiation

Popis výsledku v původním jazyce

The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes. Gas-permeable cultuware was employed to cultivate 3T3-L1 adipocytes in hypoxia (4%) for 7 or 14 days of differentiation. We investigated the contribution of glutamine, glucose or acetate using (13)C or (14)C labelled carbons to the newly synthesized lipid pool, changes in intracellular lipid content after inhibiting citrate- or acetate-dependent pathways and gene expression of involved key enzymes. The results demonstrate that, in differentiating adipocytes, hypoxia decreased the synthesis of lipids from glucose (44.1 +- 8.8 to 27.5 +- 3.0 pmol/mg of protein, p &lt; 0.01) and partially decreased the contribution of glutamine metabolized through the reverse tricarboxylic acid cycle (4.6% +- 0.2-4.2% +- 0.1%, p &lt; 0.01). Conversely, the contribution of acetate, a citrate- and mitochondria-independent source of carbons, increased upon hypoxia (356.5 +- 71.4 to 649.8 +- 117.5 pmol/mg of protein, p &lt; 0.01). Further, inhibiting the citrate- or acetate-dependent pathways decreased the intracellular lipid content by 58% and 73%, respectively (p &lt; 0.01) showing the importance of de novo lipogenesis in hypoxia-exposed adipocytes. Altogether, hypoxia modified the utilization of carbon sources, leading to alterations in de novo lipogenesis in differentiating adipocytes and increased intracellular lipid content.

Název v anglickém jazyce

Contribution of glucose and glutamine to hypoxia-induced lipid synthesis decreases, while contribution of acetate increases, during 3T3-L1 differentiation

Popis výsledku anglicky

The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes. Gas-permeable cultuware was employed to cultivate 3T3-L1 adipocytes in hypoxia (4%) for 7 or 14 days of differentiation. We investigated the contribution of glutamine, glucose or acetate using (13)C or (14)C labelled carbons to the newly synthesized lipid pool, changes in intracellular lipid content after inhibiting citrate- or acetate-dependent pathways and gene expression of involved key enzymes. The results demonstrate that, in differentiating adipocytes, hypoxia decreased the synthesis of lipids from glucose (44.1 +- 8.8 to 27.5 +- 3.0 pmol/mg of protein, p &lt; 0.01) and partially decreased the contribution of glutamine metabolized through the reverse tricarboxylic acid cycle (4.6% +- 0.2-4.2% +- 0.1%, p &lt; 0.01). Conversely, the contribution of acetate, a citrate- and mitochondria-independent source of carbons, increased upon hypoxia (356.5 +- 71.4 to 649.8 +- 117.5 pmol/mg of protein, p &lt; 0.01). Further, inhibiting the citrate- or acetate-dependent pathways decreased the intracellular lipid content by 58% and 73%, respectively (p &lt; 0.01) showing the importance of de novo lipogenesis in hypoxia-exposed adipocytes. Altogether, hypoxia modified the utilization of carbon sources, leading to alterations in de novo lipogenesis in differentiating adipocytes and increased intracellular lipid content.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/NU21-01-00259" target="_blank" >NU21-01-00259: Nové inhibitory lipolýzy v léčbě poruch metabolismu lipidů a glukózy při syndromu obstrukční spánkové apnoe</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

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

14

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

28193

Kód UT WoS článku

001356230100037

EID výsledku v databázi Scopus

2-s2.0-85209079353