Abstract
Isorhamnetin (ISOR), 3-O-methylquercetin, is a naturally occurring flavonoid in many plants. It is a metabolite derived from quercetin and is known to exert beneficial effects on the prevention of obesity. However, the molecular mechanism of action involved in ISOR-mediated mitochondrial biogenesis, and AMP-activated protein kinase (AMPK) activation in 3T3-L1 cells remains unclear. The aim of this study was to determine whether ISOR affected mitochondrial biogenesis and AMPK activation, during 3T3-L1 adipocyte differentiation. Intracellular lipid and triglyceride accumulation, and glycerol-3-phosphate dehydrogenase (GPDH) activity decreased in ISOR-treated cells. The mRNA levels of adipogenic genes, such as the proliferator-activated receptor-γ (PPAR-γ), and adipocyte protein 2 (aP2), were inhibited by ISOR. In contrast, mRNA levels of mitochondrial genes, such as peroxisome proliferator-activated reporter gamma coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, transcription factor A (Tfam), and carnitine palmitoyl transferase-1α (CPT-1α), were all stimulated by ISOR treatment. Mitochondria DNA (mtDNA) copy number and AMPK activity were also stimulated by ISOR. The results suggested that the mitochondrial biogenic effect of ISOR in adipocytes might have been associated with stimulation of mitochondrial gene expression, mtDNA replication, and AMPK activation.
Highlights
Adipose tissue is an endocrine type of tissue that plays a central role in regulating energy homeostasis
ISOR was tested for the potential cytotoxic effects it might exert on 3T3-L1 cells
There were no cytotoxic effects caused by ISOR at 0.1, 0.5, 1, 10, or 20 μM, after through downregulation of PPAR-γ and CCAAT/enhancer binding protein-α (CEBP-α) in 3T3-L1 adipocytes
Summary
Adipose tissue is an endocrine type of tissue that plays a central role in regulating energy homeostasis. Mitochondrial dysfunction in adipose tissue can lead to lipodystrophy syndrome, with metabolic and cardiovascular complications [1]. Mitochondrial dysfunction in various tissues is associated with the development of obesity and type-2 diabetes [2,3]. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is considered the metabolic regulator of mitochondrial biogenesis [5]. PGC-1α regulates mitochondrial biogenesis and function through induction of the expression of nuclear respiratory factors, NRF-1 and NRF-2 [6,7]. PGC-1α indirectly regulates the expression of mitochondria DNA (mtDNA) transcription by increasing the expression of mitochondrial transcription factor A (Tfam) [7,8]. There has been increasing interest in the regulation of mitochondrial function to prevent obesity
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