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Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
Generation of novel long-acting globular adiponectin molecules
Hongfei Ge1, Yumei Xiong, Bryan Lemon
1Amgen Inc., 1120 Veterans Blvd., South San Francisco, CA 94080, USA.
Journal of Molecular Biology
|April 13, 2010
Summary
Researchers developed single-chain globular adiponectin (sc-gAd) for improved glucose homeostasis. Fc-fused sc-gAd demonstrated a prolonged half-life and enhanced glucose tolerance in mice, offering therapeutic potential.
Area of Science:
- Metabolic regulation
- Protein engineering
- Pharmacology
Background:
- Adiponectin is a key hormone regulating glucose and energy balance.
- Recombinant adiponectin production is challenging for research and therapeutics.
- Adiponectin circulates as trimers or larger complexes.
Purpose of the Study:
- To develop a novel method for producing globular adiponectin.
- To enhance the pharmacokinetic properties of adiponectin for therapeutic use.
- To evaluate the efficacy of engineered adiponectin in a mouse model of obesity and diabetes.
Main Methods:
- Constructed single-chain globular adiponectin (sc-gAd) by linking three monomer sequences.
- Fused sc-gAd to an Fc fragment to create Fc-sc-gAd.
- Administered Fc-sc-gAd via adeno-associated virus in ob/ob mice.
Main Results:
- Fc-sc-gAd exhibited a plasma half-life extended to nearly two weeks.
- Fc-sc-gAd treatment improved fasting glucose levels in ob/ob mice.
- Glucose tolerance was enhanced in treated mice without affecting body weight.
Conclusions:
- A single polypeptide can be engineered to form functional globular adiponectin trimers.
- Fc-sc-gAd represents a promising long-acting adiponectin therapeutic candidate.
- This approach may be applicable to other C1q family proteins, enabling study of heterotrimers.
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