During
obesity adipose tissue abundantly secrete pro-inflammatory
adipokines like Tumour
Necrosis factor-alpha (TNFα),
resistin,
leptin, etc. but reduced anti-inflammatory
adipokines like
adiponectin,
interleukin (IL)-10, and
IL-4. In our recent clinical study, it was observed that both gene expressions and stored levels of
resistin were elevated in adipose tissue of metabolically obese Indians.
Resistin profoundly increases
obesity, mitigates lipid metabolism, and causes peripheral
insulin resistance. It dysregulates the metabolism of human adipocytes but, its effects on human adipose-derived mesenchymal stem cells (hADSC) are sparsely explored. Therefore, the present study was designed to explore the repercussion of
resistin on stemness and metabolic profile of hADSC. hADSC were isolated from a healthy individual followed by immunophenotyping. Purified cells were treated with
resistin and proliferation was monitored by
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Cell Cycle experiments. Gene expressions of pluripotent markers, inflammatory mediators, and lipogenic genes were scrutinized.
Insulin sensitivity was examined by western blot and
glucose uptake assay. Further, consequences of
resistin on differentiation potentials of hADSC were examined by temporal expressions of phospho (p)SMAD1/5/8
protein complex, non-phosphorylated beta (β)
catenin, and their dependent adipogenic
transcription factors (ATF) and osteogenic
transcription factors (OTF). MTT and cell cycle analysis revealed that
resistin hampered proliferation of hADSC. Expressions of inflammatory markers and lipogenic genes were elevated.
Resistin impaired
insulin sensitivity and thus embarked
insulin resistance in hADSC.
Resistin increased adipogenesis and osteogenesis by altering expressions of activated pSMAD1/5/8 complex, activated β
catenin, ATF and OTF temporally. Downregulation of
CCAAT/enhancer-binding proteins (C/EBP)α and
adiponectin in adipocytes and
Sirtuin (
SIRT)1 in osteocytes denote that
resistin induces immaturity and
insulin resistance in adipocytes and osteocytes. This is the first study which, reports that
resistin mitigates the stemness of hADSC by reducing proliferation, inducing
insulin resistance, and hampering maturation of adipocyte and osteocyte which could lead to metabolic disorders.