MA-[D-Leu-4)-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic, Improves Serum Lipid Profiles in Mouse Models of Type 1 and Type 2 Diabetes Mellitus

Diabetic dyslipidemia, a common pattern of lipid abnormalities associated with diabetes, is characterized by hyperglycemia, elevated serum levels of triglycerides and low-density lipoprotein (LDL)-cholesterol, and reduced serum levels of high-density lipoprotein (HDL)-cholesterol. These lipid abnorm...

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Bibliographic Details
Published in:International journal of peptide research and therapeutics 2021-06, Vol.27 (2), p.1121-1128
Main Authors: Hirschstein, Zall, Wang, Anke, Anderson, Brian M., Novakovic, Zachary M., Grasso, Patricia
Format: Article
Language:English
Subjects:
Animal Anatomy
Animal models
Biochemistry
Biomedical and Life Sciences
Cardiovascular diseases
Cholesterol
Cognitive ability
Diabetes
Diabetes mellitus (insulin dependent)
Diabetes mellitus (non-insulin dependent)
Dyslipidemia
Energy balance
High density lipoprotein
High fat diet
Histology
Hyperglycemia
Insulin
Leptin
Life Sciences
Lipids
Lipoproteins (very low density)
Low density lipoprotein
Metabolic disorders
Molecular Medicine
Morphology
Pharmaceutical Sciences/Technology
Pharmacology/Toxicology
Polymer Sciences
Serum levels
Streptozocin
Triglycerides
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Summary:Diabetic dyslipidemia, a common pattern of lipid abnormalities associated with diabetes, is characterized by hyperglycemia, elevated serum levels of triglycerides and low-density lipoprotein (LDL)-cholesterol, and reduced serum levels of high-density lipoprotein (HDL)-cholesterol. These lipid abnormalities make diabetes an independent risk-factor for the development of cardiovascular disease. Two mouse models of diabetes were used in the present study: 1) streptozotocin (STZ)-induced insulin-deficient male Swiss Webster mice (a model of T1DM), and 2) male diet-induced obese (DIO) mice rendered insulin-resistant by maintenance on a high-fat diet for 30 weeks (a model of T2DM). Both models were then treated with MA-[D-Leu-4]-OB3 by oral gavage for 14 or 17 days. At the end of the test period, the mice were exsanguinated by cardiac puncture; serum was prepared from the whole blood and analyzed by ELISA for total-, HDL-, LDL/VLDL-cholesterol, and triglyceride content. In mouse models of both T1DM and T2DM, MA-[D-Leu-4]-OB3 significantly (P 
ISSN:1573-3149
1573-3904
DOI:10.1007/s10989-020-10155-y