Prophylactic Application of MA-[d-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic, Prevents or Slows the Progression of Obesity, Insulin Resistance, and Cognitive Impairment in a Mouse Model of Type 2 Diabetes Mellitus
Oral delivery of MA-[ d -Leu-4]-OB3 has been shown to significantly improve energy balance, glycemic control, dyslipidemia, and episodic memory in mouse models of fully-expressed T1DM and T2DM. To assess the prophylactic capacity of MA-[ d -Leu-4]-OB3 to prevent or slow the progression of obesity, i...
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Published in | International journal of peptide research and therapeutics Vol. 27; no. 4; pp. 2223 - 2230 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Dordrecht
Springer Netherlands
01.12.2021
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Oral delivery of MA-[
d
-Leu-4]-OB3 has been shown to significantly improve energy balance, glycemic control, dyslipidemia, and episodic memory in mouse models of fully-expressed T1DM and T2DM. To assess the prophylactic capacity of MA-[
d
-Leu-4]-OB3 to prevent or slow the progression of obesity, insulin resistance, and cognitive dysfunction, 3- to 4-week old male C57BL/6J mice were placed on a high-fat diet immediately after weaning, and maintained on this diet, in the absence or presence of orally delivered MA-[
d
-Leu-4]-OB3, for 23 weeks. Control mice of the same age and sex were maintained on a low-fat diet. Body weight, caloric and water intake, glucose tolerance, and fasting blood glucose levels were measured. Episodic memory was evaluated by novel object recognition testing. In male C57BL/6J mice maintained on a high-fat diet since weaning, MA-[
d
-Leu-4]-OB3 (1) normalized body weight gain for the first 8 weeks of the study, and sustained a significant reduction throughout the remaining 15 weeks; (2) had no effect on caloric or water intake; (3) improved glucose tolerance within 4 weeks; (4) reduced fasting blood glucose to levels approaching or equivalent to those seen in control mice within 3 weeks; and (5) normalized episodic memory within 4 weeks. In addition to its therapeutic potential, MA-[
d
-Leu-4]-OB3 may have a prophylactic application to the prevention or progression of many of the dysfunctions associated with metabolic syndrome, Down Syndrome, Alzheimer’s disease (AD), and other AD-like cognitive impairments in humans. |
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ISSN: | 1573-3149 1573-3904 |
DOI: | 10.1007/s10989-021-10248-2 |