TY - JOUR
T1 - β-Cyclodextrin counteracts obesity in Western diet-fed mice but elicits a nephrotoxic effect
AU - Scantlebery, Angelique M. L.
AU - Ochodnicky, Peter
AU - Kors, Lotte
AU - Rampanelli, Elena
AU - Butter, Loes M.
AU - el Boumashouli, Chaima
AU - Claessen, Nike
AU - Teske, Gwen J.
AU - van den Bergh Weerman, Marius A.
AU - Leemans, Jaklien C.
AU - Roelofs, Joris J. T. H.
AU - Florquin, Sandrine
PY - 2019
Y1 - 2019
N2 - Obesity has become a worldwide health crisis and is associated with a plethora of comorbidities. The multi-organ effects of obesity have been linked to ectopic lipid accumulation. Thus, there is an urgent need to tackle the obesity crisis by developing effective lipid-lowering therapies. 2-hydroxypropyl-β-Cyclodextrin (2HP-β-CD) has been previously shown to reduce lysosomal cholesterol accumulation in a murine model of Niemann Pick Type C (NPC) disease. Using a murine model of Western diet-induced obesity (DIO), we report the effects of 2HP-β-CD in counteracting weight gain, expansion of adipose tissue mass and ectopic lipid accumulation. Interestingly, DIO caused intracellular storage of neutral lipids in hepatic tissues and of phospholipids in kidneys, both of which were prevented by 2HP-β-CD. Importantly, this report brings attention to the nephrotoxic effects of 2HP-β-CD: renal tubular damage, inflammation and fibrosis. These effects may be overlooked, as they are best appreciated upon assessment of renal histology.
AB - Obesity has become a worldwide health crisis and is associated with a plethora of comorbidities. The multi-organ effects of obesity have been linked to ectopic lipid accumulation. Thus, there is an urgent need to tackle the obesity crisis by developing effective lipid-lowering therapies. 2-hydroxypropyl-β-Cyclodextrin (2HP-β-CD) has been previously shown to reduce lysosomal cholesterol accumulation in a murine model of Niemann Pick Type C (NPC) disease. Using a murine model of Western diet-induced obesity (DIO), we report the effects of 2HP-β-CD in counteracting weight gain, expansion of adipose tissue mass and ectopic lipid accumulation. Interestingly, DIO caused intracellular storage of neutral lipids in hepatic tissues and of phospholipids in kidneys, both of which were prevented by 2HP-β-CD. Importantly, this report brings attention to the nephrotoxic effects of 2HP-β-CD: renal tubular damage, inflammation and fibrosis. These effects may be overlooked, as they are best appreciated upon assessment of renal histology.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85075734841&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31776357
U2 - https://doi.org/10.1038/s41598-019-53890-z
DO - https://doi.org/10.1038/s41598-019-53890-z
M3 - Article
C2 - 31776357
SN - 2045-2322
VL - 9
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 17633
ER -