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Ablation of AMPK-Related Kinase MPK38/MELK Leads to Male-Specific Obesity in Aged Mature Adult Mice
- Source :
- Diabetes. 70(2)
- Publication Year :
- 2020
-
Abstract
- Murine protein serine-threonine kinase 38 (MPK38)/maternal embryonic leucine zipper kinase (MELK) is implicated in diverse biological processes, including the cell cycle, apoptosis, and tumorigenesis; however, its physiological role is unknown. Using mice lacking MPK38 (MPK38−/−), we found that MPK38−/− male, but not female, mice (7 months of age) became obese while consuming a standard diet, displayed impairments in metabolism and inflammation, became more obese than wild-type mice while consuming a high-fat diet, and exhibited no castration/testosterone replacement–induced metabolic changes. The adenoviral restoration of MPK38 ameliorated the obesity-induced adverse metabolic profile of the obese male, but not female, mice. Seven-month-old MPK38−/− males displayed typical postcastration concentrations of serum testosterone with an accompanying decrease in serum luteinizing hormone (LH) levels, suggesting a role for MPK38 in the age-related changes in serum testosterone in aged mature adult male mice. The stability and activity of MPK38 were increased by dihydrotestosterone but reduced by estradiol (E2). These findings suggest MPK38 as a therapeutic target for obesity-related metabolic disorders in males.
- Subjects :
- 0301 basic medicine
Blood Glucose
Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Inflammation
Fatty Acids, Nonesterified
Protein Serine-Threonine Kinases
Diet, High-Fat
Maternal embryonic leucine zipper kinase
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Sex Factors
Internal medicine
Internal Medicine
medicine
Animals
Insulin
Testosterone
Obesity
Phosphorylation
Mice, Knockout
Estradiol
business.industry
Kinase
Lipogenesis
AMPK
Glucose Tolerance Test
Luteinizing Hormone
030104 developmental biology
Endocrinology
Castration
chemistry
Apoptosis
Dihydrotestosterone
Female
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 1939327X
- Volume :
- 70
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....63174011b0beddcac9eca2dd92dd3f3e