Estradiol overcomes adiponectin-resistance in diabetic mice by regulating skeletal muscle adiponectin receptor 1 expression. (15th January 2022)

• Record Type: Journal Article
• Authors: Chattopadhyay, Sourav; Joharapurkar, Amit; Das, Nabanita; Khatoon, Shamima; Kushwaha, Sapana; Gurjar, Anagha Ashok; Singh, Abhishek Kumar; Shree, Sonal; Ahmed, Md Zohaib; China, Shyamsundar Pal; Pal, Subhashis; Kumar, Harish; Ramachandran, Ravishankar; Patel, Vishal; Trivedi, Arun Kumar; Lahiri, Amit; Jain, Mukul Rameshchandra; Chattopadhyay, Naibedya; Sanyal, Sabyasachi
• Is Part Of: Molecular and cellular endocrinology. Volume 540(2022)
• Publication Date: 2022-01-15
• Subjects: Adiponectin -- AdipoR -- Estradiol -- Estrogen receptor -- PTBP1 -- miR-221; BKS-db/db: Leptin receptor-deficient diabetic (db/db) mice in BLKS background E2 -- 17-beta Estradiol gAd -- Globular adiponectin AdipoR1 -- adiponectin receptor 1 miR-221 -- micro RNA-221 PTB -- polypyrimidine tract binding protein 1 ER -- estrogen receptors AMPK -- AMP-dependent protein kinase AKT -- Protein Kinase B P38 MAPK -- p38 mitogen-activated protein kinase CD36 -- Cluster of differentiation 36/fatty acid translocase PPAR α -- peroxisome proliferator-activated receptor α PGC-1α -- PPAR gamma co activator 1-α Glut4 -- glucose transporter type 4 UCP3 -- uncoupling protein 3 GAPDH -- Glyceraldehyde 3-phosphate dehydrogenase Ovx: Ovariectomy; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2021.111525
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Adiponectin and insulin resistance creates a vicious cycle that exacerbates type 2 diabetes. Earlier, we observed that female leptin receptor-deficient BLKS mice (BKS-db/db) were more sensitive to an adiponectin mimetic GTDF than males, which led us to explore if E2 plays a crucial role in modulation of adiponectin-sensitivity. Male but not female BKS-db/db mice were resistant to metabolic effects of globular adiponectin treatment. Male BKS-db/db displayed reduced skeletal muscle AdipoR1 protein expression, which was consequent to elevated polypyrimidine tract binding protein 1 (PTB) and miR-221. E2 treatment in male BKS-db/db, and ovariectomized BALB/c mice rescued AdipoR1 protein expression via downregulation of PTB and miR-221, and also directly increased AdipoR1 mRNA by its classical nuclear receptors. Estrogen receptor regulation via dietary or pharmacological interventions may improve adiponectin resistance and consequently ameliorate insulin resistance in type 2 diabetes. Graphical abstract: Image 1 Highlights: Male but not female BKS-db/db mice are resistant to globular adiponectin treatment. Male BKS-db/db display reduced skeletal muscle AdipoR1 and elevated PTB and miR-221. E2 treatment in male BKS-db/db ameliorates globular adiponectin resistance. Ovariectomy induces adiponectin resistance and estradiol treatment improves it. Estradiol imparts adiponectin sensitivity via its classical nuclear receptors.