TY - JOUR
T1 - Disruption of lateral hypothalamic calorie detection by a free choice high fat diet
AU - Koekkoek, Laura L.
AU - Slomp, Margo
AU - Castel, Julien
AU - Mutersbaugh, Michael
AU - Linville, Ian
AU - Serlie, Mireille J.
AU - Luquet, Serge H.
AU - la Fleur, Susanne E.
N1 - Funding Information: We thank Dr Y. Aponte for kindly providing the infrastructure for this study and S. Sarsfield for assistance with histology and imaging. We thank C. Cover for his assistance with the building and use of the lickometer. We thank Dr. R. Holman for her assistance with the statistical analysis. Lastly, we thank prof. D. Small for her critical reading of the manuscript. This work was supported by an AMC PhD fellowship grant awarded by the AMC Executive Board and by the Netherlands Organization of Scientific Research (NWO‐VICI grant 016.160.617). Funding Information: We thank Dr Y. Aponte for kindly providing the infrastructure for this study and S. Sarsfield for assistance with histology and imaging. We thank C. Cover for his assistance with the building and use of the lickometer. We thank Dr. R. Holman for her assistance with the statistical analysis. Lastly, we thank prof. D. Small for her critical reading of the manuscript. This work was supported by an AMC PhD fellowship grant awarded by the AMC Executive Board and by the Netherlands Organization of Scientific Research (NWO-VICI grant 016.160.617). Publisher Copyright: © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology
PY - 2021/9/1
Y1 - 2021/9/1
N2 - During the last few decades, the consumption of low-calorie sweeteners, as a substitute for caloric sweeteners, has sharply increased. Although research shows that caloric versus low-calorie sweeteners can have differential effects on the brain, it is unknown which neuronal populations are responsible for detecting the difference between the two types of sweeteners. Using in vivo two-photon calcium imaging, we investigated how drinking sucrose or sucralose (a low-calorie sweetener) affects the activity of glutamatergic neurons in the lateral hypothalamus. Furthermore, we explored the consequences of consuming a free-choice high fat diet on the calorie detection abilities of these glutamatergic neurons. We found that glutamatergic neurons indeed can discriminate sucrose from water and sucralose, and that consumption of a free-choice high fat diet shifts the glutamatergic neuronal response from sucrose-specific to sucralose-specific, thereby disrupting calorie detection. These results highlight the disruptive effects of a diet high in saturated fat on calorie detection in the lateral hypothalamus.
AB - During the last few decades, the consumption of low-calorie sweeteners, as a substitute for caloric sweeteners, has sharply increased. Although research shows that caloric versus low-calorie sweeteners can have differential effects on the brain, it is unknown which neuronal populations are responsible for detecting the difference between the two types of sweeteners. Using in vivo two-photon calcium imaging, we investigated how drinking sucrose or sucralose (a low-calorie sweetener) affects the activity of glutamatergic neurons in the lateral hypothalamus. Furthermore, we explored the consequences of consuming a free-choice high fat diet on the calorie detection abilities of these glutamatergic neurons. We found that glutamatergic neurons indeed can discriminate sucrose from water and sucralose, and that consumption of a free-choice high fat diet shifts the glutamatergic neuronal response from sucrose-specific to sucralose-specific, thereby disrupting calorie detection. These results highlight the disruptive effects of a diet high in saturated fat on calorie detection in the lateral hypothalamus.
KW - calorie detection
KW - glutamate
KW - hypothalamus
KW - low-calorie sweetener
KW - two-photon microscopy
UR - http://www.scopus.com/inward/record.url?scp=85113507449&partnerID=8YFLogxK
U2 - https://doi.org/10.1096/fj.202100762R
DO - https://doi.org/10.1096/fj.202100762R
M3 - Article
C2 - 34383974
SN - 0892-6638
VL - 35
JO - FASEB Journal
JF - FASEB Journal
IS - 9
M1 - e21804
ER -