TY - JOUR
T1 - Sustained insulin treatment restoring metabolic status, body weight, and cognition in an anorexia nervosa-like animal model in mice
AU - Avraham, Yosefa
AU - Shapira-Furman, Tovi
AU - Saklani, Ravi
AU - Van Heukelom, Bob
AU - Carmel, Moshe
AU - Vorobiev, Lia
AU - Lipsker, Leah
AU - Zwas, Donna R.
AU - Berry, Elliot M.
AU - Domb, Abraham J.
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/5/28
Y1 - 2024/5/28
N2 - Introduction: Anorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment. Methods: AN-like model was established through dietary restriction (DR). On days 1–25, mice were on DR, and on days 26–31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function. Results: The delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model. Conclusion: The PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment."
AB - Introduction: Anorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment. Methods: AN-like model was established through dietary restriction (DR). On days 1–25, mice were on DR, and on days 26–31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function. Results: The delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model. Conclusion: The PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment."
KW - Animal Model
KW - Anorexia Nervosa
KW - Cognition
KW - Drug Delivery
KW - Gene expression
KW - Insulin
UR - http://www.scopus.com/inward/record.url?scp=85190866394&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2024.115001
DO - 10.1016/j.bbr.2024.115001
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C2 - 38642861
AN - SCOPUS:85190866394
SN - 0166-4328
VL - 466
JO - Behavioural Brain Research
JF - Behavioural Brain Research
M1 - 115001
ER -