Estradiol overcomes adiponectin-resistance in diabetic mice by regulating skeletal muscle adiponectin receptor 1 expression

Sourav Chattopadhyay, Amit Joharapurkar, Nabanita Das, Shamima Khatoon, Sapana Kushwaha, Anagha Ashok Gurjar, Abhishek Kumar Singh, Sonal Shree, Md Zohaib Ahmed, Shyamsundar Pal China, Subhashis Pal, Harish Kumar, Ravishankar Ramachandran, Vishal Patel, Arun Kumar Trivedi, Amit Lahiri, Mukul Rameshchandra Jain, Naibedya Chattopadhyay, Sabyasachi Sanyal

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Article number111525
JournalMolecular and Cellular Endocrinology
Volume540
DOIs
StatePublished - 15 Jan 2022
Externally publishedYes

Keywords

  • AdipoR
  • Adiponectin
  • Estradiol
  • Estrogen receptor
  • PTBP1
  • miR-221

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