Obesity and type 2 diabetes are two interrelated kinds of metabolic diseases which do serious harm to the health of contemporary population, and it can lead to coronary heart disease, stroke, fatty liver, neurodegenerative and other complications. If we can try to balance the energy consumption-intake trend more toward the consumption of this end of the tilt, then it will be able to significantly alleviate the symptoms of the disease. White adipose tissue is the main place to store fat in the human body. It can produce "browning" under specific stimulation, which is similar to the metabolic characteristics of brown adipose tissue - high energy consumption and heat production. Therefore, if the white adipose tissue can change the metabolic characteristics, it tends to "brown", will be expected to play a therapeutic effect.
More recently, Prof. Anutosh Chakraborty from the Scripps Research Institute (University of Florida) found a target protein, hexose inositol phosphokinase 1 (IP6K1), which is expected to be used to achieve this effect. Using recombinant rat proteins, they found that IP6K1 itself can affect the metabolic pathway of fat cells regulated by AMPK, which slows down the decomposition and consumption of fat in the body, thus accelerating the accumulation of fat. The results were published in the recent issue of The Journal of Clinical Investigation.
"We found IP6K1 to be a suitable therapeutic target for obesity and type 2 diabetes," said Professor Chakraborty. "We also found that TNP, an inhibitor of IP6K1, alleviates dietary-induced obesity and insulin resistance."
IP6K1 may have a significant effect on the metabolic pattern of white adipose tissue. Its substrate phytate (IP6) promotes AMPK phosphorylation, thereby upregulating PGC1α transcription coactivator and uncoupling protein 1 (UCP1) -mediated thermogenesis in promoting white adipose tissue browning. IP6K1 converts IP6 to inositol hexaphosphate (5-IP7), which no longer activates AMPK, and it inhibits Akt kinases that promote browning at the same time.
Mouse experiments show that cold stimulation can reduce the white adipose tissue IP6K1 levels, thereby increasing the decomposition of fat at this time of heat. When IP6K1 was knocked out in white adipose tissue, the activity of AMPK was increased, and the heat of lipolysis was enhanced significantly. The white adipose tissue showed browning characteristics, including the elevation of browning marker proteins such as UCP1 and PGC1α. When this IP6K1 knockout mouse received a high-fat diet, the propensity to develop obesity and insulin resistance was significantly reduced. The researchers further found that IP6K1 inhibitor TNP in mice can play a similar effect.
"In addition, TNP also promotes weight loss in mice and improves metabolic markers in obese mice," said Professor Chakraborty. Flarebio offers recombinant proteins such as recombinant App at competitive prices.
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