TY - JOUR
T1 - Chronic agmatine treatment prevents olanzapine-induced obesity and metabolic dysregulation in female rats
AU - Dixit, Madhura P
AU - Sammeta, Shivkumar S
AU - Dhokne, Mrunali D
AU - Mangrulkar, Shubhada
AU - Upadhya, Manoj A
AU - Umekar, Milind J
AU - Taksande, Brijesh G
AU - Kotagale, Nandkishor R
N1 - Copyright © 2022, Elsevier Inc. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Antipsychotic-induced obesity affects millions of people and is a serious health condition worldwide. Olanzapine is the most widely prescribed antipsychotic agent with high obesogenic potential. However, the exact mechanism by which it causes its metabolic dysregulation remains poorly understood. In this study, we investigated the effect of agmatine in olanzapine-induced metabolic derangements in Female Sprague-Dawley rats. Repeated olanzapine administration for 28 days increased body weight while treatment with agmatine from days 15 to 28 prevented the body weight gain induced by olanzapine without any alteration in food intake. Repeated agmatine treatment decreased the elevated feeding efficiency and adiposity index, as well as improved dysregulated lipid metabolism induced by olanzapine. Increased activity of fatty acid synthase (FAS) and decreased expression of carnitine palmitoyl transferase-1 (CPT-1) were detected in chronic olanzapine-treated rats. Although agmatine treatment did not alter FAS activity, it increased CPT-1 activity. It is possible that the inhibitory effect of agmatine on weight gain and adiposity might be associated with increased mitochondrial fatty acid oxidation and energy expenditure in olanzapine-treated rats. We suggest that agmatine can be explored for the prevention of obesity complications associated with chronic antipsychotic treatment.
AB - Antipsychotic-induced obesity affects millions of people and is a serious health condition worldwide. Olanzapine is the most widely prescribed antipsychotic agent with high obesogenic potential. However, the exact mechanism by which it causes its metabolic dysregulation remains poorly understood. In this study, we investigated the effect of agmatine in olanzapine-induced metabolic derangements in Female Sprague-Dawley rats. Repeated olanzapine administration for 28 days increased body weight while treatment with agmatine from days 15 to 28 prevented the body weight gain induced by olanzapine without any alteration in food intake. Repeated agmatine treatment decreased the elevated feeding efficiency and adiposity index, as well as improved dysregulated lipid metabolism induced by olanzapine. Increased activity of fatty acid synthase (FAS) and decreased expression of carnitine palmitoyl transferase-1 (CPT-1) were detected in chronic olanzapine-treated rats. Although agmatine treatment did not alter FAS activity, it increased CPT-1 activity. It is possible that the inhibitory effect of agmatine on weight gain and adiposity might be associated with increased mitochondrial fatty acid oxidation and energy expenditure in olanzapine-treated rats. We suggest that agmatine can be explored for the prevention of obesity complications associated with chronic antipsychotic treatment.
KW - Olanzapine
KW - Agmatine
KW - Antipsychotics-induced obesity
KW - Metabolic syndrome
UR - https://www.sciencedirect.com/science/article/abs/pii/S0361923022002830?via%3Dihub
UR - http://www.scopus.com/inward/record.url?scp=85140903886&partnerID=8YFLogxK
U2 - 10.1016/j.brainresbull.2022.10.013
DO - 10.1016/j.brainresbull.2022.10.013
M3 - Article
C2 - 36272666
SN - 0361-9230
VL - 191
SP - 69
EP - 77
JO - Brain research bulletin
JF - Brain research bulletin
ER -