DACRA induces profound weight loss, satiety control, and increased mitochondrial respiratory capacity in adipose tissue
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DACRA induces profound weight loss, satiety control, and increased mitochondrial respiratory capacity in adipose tissue. / Petersen, Emilie A.; Blom, Ida; Melander, Simone A.; Al-Rubai, Mays; Vidotto, Marina; Dalgaard, Louise T.; Karsdal, Morten A.; Henriksen, Kim; Larsen, Steen; Larsen, Anna T.
In: International Journal of Obesity, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - DACRA induces profound weight loss, satiety control, and increased mitochondrial respiratory capacity in adipose tissue
AU - Petersen, Emilie A.
AU - Blom, Ida
AU - Melander, Simone A.
AU - Al-Rubai, Mays
AU - Vidotto, Marina
AU - Dalgaard, Louise T.
AU - Karsdal, Morten A.
AU - Henriksen, Kim
AU - Larsen, Steen
AU - Larsen, Anna T.
N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature Limited 2024.
PY - 2024
Y1 - 2024
N2 - Background and objectives: Dual amylin and calcitonin receptor agonists (DACRAs) are therapeutic candidates in the treatment of obesity with beneficial effects on weight loss superior to suppression of food intake. Hence, suggesting effects on energy expenditure by possibly targeting mitochondria in metabolically active tissue. Methods: Male rats with HFD-induced obesity received a DACRA, KBP-336, every third day for 8 weeks. Upon study end, mitochondrial respiratory capacity (MRC), - enzyme activity, - transcriptional factors, and -content were measured in perirenal (pAT) and inguinal adipose tissue. A pair-fed group was included to examine food intake-independent effects of KBP-336. Results: A vehicle-corrected weight loss (23.4 ± 2.8%) was achieved with KBP-336, which was not observed to the same extent with the food-restricted weight loss (12.4 ± 2.8%) (P < 0.001). Maximal coupled respiration supported by carbohydrate and lipid-linked substrates was increased after KBP-336 treatment independent of food intake in pAT (P < 0.01). Moreover, oligomycin-induced leak respiration and the activity of citrate synthase and β-hydroxyacetyl-CoA-dehydrogenase were increased with KBP-336 treatment (P < 0.05). These effects occurred without changes in mitochondrial content in pAT. Conclusions: These findings demonstrate favorable effects of KBP-336 on MRC in adipose tissue, indicating an increased energy expenditure and capacity to utilize fatty acids. Thus, providing more mechanistic insight into the DACRA-induced weight loss. (Figure presented.)
AB - Background and objectives: Dual amylin and calcitonin receptor agonists (DACRAs) are therapeutic candidates in the treatment of obesity with beneficial effects on weight loss superior to suppression of food intake. Hence, suggesting effects on energy expenditure by possibly targeting mitochondria in metabolically active tissue. Methods: Male rats with HFD-induced obesity received a DACRA, KBP-336, every third day for 8 weeks. Upon study end, mitochondrial respiratory capacity (MRC), - enzyme activity, - transcriptional factors, and -content were measured in perirenal (pAT) and inguinal adipose tissue. A pair-fed group was included to examine food intake-independent effects of KBP-336. Results: A vehicle-corrected weight loss (23.4 ± 2.8%) was achieved with KBP-336, which was not observed to the same extent with the food-restricted weight loss (12.4 ± 2.8%) (P < 0.001). Maximal coupled respiration supported by carbohydrate and lipid-linked substrates was increased after KBP-336 treatment independent of food intake in pAT (P < 0.01). Moreover, oligomycin-induced leak respiration and the activity of citrate synthase and β-hydroxyacetyl-CoA-dehydrogenase were increased with KBP-336 treatment (P < 0.05). These effects occurred without changes in mitochondrial content in pAT. Conclusions: These findings demonstrate favorable effects of KBP-336 on MRC in adipose tissue, indicating an increased energy expenditure and capacity to utilize fatty acids. Thus, providing more mechanistic insight into the DACRA-induced weight loss. (Figure presented.)
U2 - 10.1038/s41366-024-01564-w
DO - 10.1038/s41366-024-01564-w
M3 - Journal article
C2 - 38879729
AN - SCOPUS:85196035506
JO - International Journal of Obesity
JF - International Journal of Obesity
SN - 0307-0565
ER -
ID: 395391752