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ABSTRACT Sirt1/AMPK and Akt/mTOR axes regulate cellular energy homeostasis and metabolism. Sodium butyrate (NaB) is a product of healthy gut microbiota and a histone deacetylase inhibitor. Recent studies have shown that NaB activates the intracellular pathways involving key metabolic regulator molecules. However, the effect of NaB on Sirt1/AMPK and Akt/mTOR axes is not reported. We compared genetic expression of Sirt1, AMPK, Akt, and mTOR in adipose tissue from mice treated with NaB versus placebo. Four groups of mice (n=27) mice were administered oral NaB, intraperitoneal (i.p) NaB, oral placebo or i.p placebo for 16 days. RNA was isolated from the epididymal fat pads and relative genetic expression of AMPK, Sirt1, mTOR and Akt was measured using real time PCR.
Oral NaB group showed decreased genetic expression of AMPK (0.04 fold, p[LESS-THAN]0.001), mTOR (0.30 fold, p=0.04), Akt (0.29 fold, p=0.67) and Sirt1 (0.83 fold, p=0.18). In the I/P group AMPK (2.26 fold, p=0.33), Akt (1.3 fold, p=0.59) and Sirt1 (1.69, p=0.45) were increased while mTOR was unchanged (0.99 fold, p=0.81). Our study for the first time reports on change in genetic expression of Sirt1/AMPK and Akt/mTOR axes in adipose tissue of mice given oral and intraperitoneal NaB treatment.
Key words Akt, mTOR, AMPK, Sirt1, Butyrate.
INTRODUCTION Cellular energy metabolism and proliferation are interdependent physiological processes. A delicate balance between the two is key for cellular homeostasis. Cells have developed signaling axes to coordinate their growth with nutrient availability. AMPK/Sirt1 axis is the key nutrient sensing axis which is activated with energy stress and nutrient depletion. It activates downstream catabolic pathways aimed at replenishing energy status. Akt/mTOR axis, on the other hand, regulates cellular proliferation in addition to metabolism. It is primarily activated by external growth factors and insulin as well as energy and nutrient availability (Yuan et al., 2013).
The Sitr1/AMPK axis includes two serine threonine kinases silent information regulator 1 (Sirt1) and AMP-activated protein kinase (AMPK). Both these molecules affect similar biological process and it has also been discovered that Sirt1 phosphorylates LKB1, the upstream kinase of AMPK and AMPK activated Sirt1 though Nampt (Cetrullo et al., 2015) AMPK is a serine threonine kinase which acts as a metabolic fuel gauge. It senses intracellular AMP/ATP ratio (Cantó et al., 2009). Typically AMPK is activated when...