Key result
Oral AdipoAI improves glucose control and reduces fat in obese mice similarly to AdipoRON.
Why the study?
There is a need for orally active small molecules that activate adiponectin receptors and downstream signaling to ameliorate obesity-related type 2 diabetes.
Does AdipoAI improve blood glucose and insulin sensitivity in diet-induced obesity mice models?
Does AdipoAI improve blood glucose and insulin sensitivity in diet-induced obesity mice models?
AdipoAI is a novel, orally active adiponectin receptor agonist that demonstrates promising antidiabetic and anti-obesity effects in preclinical models.
AdipoAI merits further development as an oral agonist; leaves open translation to human metabolic disease.
Adiponectin is an antidiabetic endogenous adipokine that plays a protective role against the unfavorable metabolic sequelae of obesity. Recent evidence suggests a sinister link between hypoadiponectinemia and development of insulin resistance/type 2 diabetes (T2D). Adiponectin's insulin-sensitizing property is mediated through the specific adiponectin receptors R1 and R2, which activate the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR) α pathways. AdipoAI is a novel synthetic analogue of endogenous adiponectin with possibly similar pharmacological effects. Thus, there is a need of orally active small molecules that activate Adipoq subunits, and their downstream signaling, which could ameliorate obesity related type 2 diabetes. In the study we aim to investigate the effects of AdipoAI on obesity and T2D. Through in-vitro and in-vivo analyses, we investigated the antidiabetic potentials of AdipoAI and compared it with AdipoRON, another orally active adiponectin receptors agonist. Our results showed that in-vitro treatment of AdipoAI (0-5 µM) increased adiponectin receptor subunits AdipoR1/R2 with increase in AMPK and APPL1 protein expression in C2C12 myotubes. Similarly, in-vivo, oral administration of AdipoAI (25 mg/kg) observed similar effects as that of AdipoRON (50 mg/kg) with improved control of blood glucose and insulin sensitivity in diet-induced obesity (DIO) mice models. Further, AdipoAI significantly reduced epididymal fat content with decrease in inflammatory markers and increase in PPAR-α and AMPK levels and exhibited hepatoprotective effects in liver. Further, AdipoAI and AdipoRON also observed similar results in adipose tissue. Thus, our results suggest that low doses of orally active small molecule agonist of adiponectin AdipoAI can be a promising therapeutic target for obesity and T2D.
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Ahuja et al. (2024) studied Obesity and Type 2 Diabetes. AdipoAI vs. AdipoRON (50 mg/kg) was evaluated on Blood glucose, insulin sensitivity, and epididymal fat content. Oral administration of AdipoAI (25 mg/kg) improved blood glucose control and insulin sensitivity, and reduced epididymal fat content in diet-induced obesity mice, similar to AdipoRON.
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