Placental mesenchymal stem cells restore glucose and energy homeostasis in obesogenic adipocytes

Nagasuryaprasad Kotikalapudi, Samuel Joshua Pragasam Sampath, Sukesh Narayan Sinha, Bhonde R, Sathish Kumar Mungamuri, Vijayalakshmi Venkatesan

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Obesity (Ob) depicts a state of energy imbalance(s) being characterized by the accumulation of excessive fat and which predisposes to several metabolic diseases. Mesenchymal stem cells (MSCs) represent a promising option for addressing obesity and its associated metabolic co-morbidities. The present study aims at assessing the beneficial effects of human placental MSCs (P-MSCs) in mitigating Ob-associated insulin resistance (IR) and mitochondrial dysfunction both in vivo and in vitro. Under obesogenic milieu, adipocytes showed a significant reduction in glucose uptake, and impaired insulin signaling with decreased expression of UCP1 and PGC1α, suggestive of dysregulated non-shivering thermogenesis vis-a-vis mitochondrial biogenesis respectively. Furthermore, obesogenic adipocytes demonstrated impaired mitochondrial respiration and energy homeostasis evidenced by reduced oxygen consumption rate (OCR) and blunted ATP/NAD+/NADP+ production respectively. Interestingly, co-culturing adipocytes with P-MSCs activated PI3K-Akt signaling, improved glucose uptake, diminished ROS production, enhanced mitochondrial OCR, improved ATP/NAD+/NADP+ production, and promoted beiging of adipocytes evidenced by upregulated expression of PRDM16, UCP1, and PGC1α expression. In vivo, P-MSCs administration increased the peripheral blood glucose uptake and clearance, and improved insulin sensitivity and lipid profile with a coordinated increase in the ratio of ATP/ADP and NAD+ and NADP+ in the white adipose tissue (WAT), exemplified in WNIN/GR-Ob obese mutant rats. In line with in vitro findings, there was a significant reduction in adipocyte hypertrophy, increased mitochondrial staining, and thermogenesis. Our findings advocate for a therapeutic application of P-MSCs for improving glucose and energy homeostasis, i.e., probably restoring non-shivering thermogenesis towards obesity management.

Original languageEnglish
Pages (from-to)127-144
Number of pages18
JournalCell and Tissue Research
Volume391
Issue number1
DOIs
StatePublished - Jan 2023
Externally publishedYes

Keywords

  • Adipocytes
  • Beiging phenotype
  • Energy homeostasis
  • Human P-MSC therapy
  • Mitochondrial turnover
  • Obesogenic milieu

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