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Fructose uptake by brown adipose tissue is independent of carbohydrate response element-binding protein and does not cause elevated de novo lipogenesis.
Acta Biochim. Biophys. Sin., DOI: 10.3724/abbs.2025229 (2025)
Brown adipose tissue (BAT) is a heat-generating organ burning significant amounts of calories from fatty acids and glucose. The importance of glucose metabolism in the context of thermogenic function has been underlined by several studies. However, fructose metabolism and consequences of fructose overfeeding are poorly studied in BAT. Here we provide evidence that brown adipocytes use fructose as a substrate, however to a lesser extent than glucose. Furthermore, our data suggest that carbohydrate response element binding protein (ChREBP) and its target glucose transporter 5 (GLUT5) are not essential for fructose uptake and metabolism in BAT. Notably, we report that high fructose feeding has no effect on ChREBP activity and thus de novo fatty acid synthesis in BAT as opposed to liver and intestine. Instead, excessive carbohydrate loading of brown adipocytes induced by both, high-fructose feeding and impairment of ChREBP-dependent glucose metabolism, causes a massive accumulation of hexosylceramide species, as revealed by mass spectrometry-based lipidomics. Based on our data we hypothesize a reprogramming of fructose utilization upon impaired carbohydrate metabolism from canonical glycolysis and pentose phosphate pathway towards glycosphingolipid synthesis.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Chrebp ; Brown Adipose Tissue ; Ceramides ; Fructose ; Lipogenesis
ISSN (print) / ISBN
1672-9145
e-ISSN
1745-7270
Publisher
Science Press
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)