NAFLD
Increased visceral (around organs) adiposity and insulin resistance (IR).Insulin resistance in the liver is associated with more hepatic glucose output due to insulin-suppressing effects on gluconeogenesis being impaired. Worsening hyperglycemia, resulting to type 2 diabetes. Peripheral IR (adipose tissue, skeletal muscle) causes increased free fatty acids (FFA) which move to the liver increased hepatic fatty acid synthesis and FFAs results in increased triglyceride accumulation in the liver. FFA re-esterification process causes long-chain acyl-CoAs and diacylglycerol (DAG) to accumulate. Excess FFAs prevents kinase interaction with phosphatidylinositol 3-kinase (PI3K) activation. The FFA-induced down-regulation of insulin signaling pathways results in several kinases involved in stress response being activated. Which will lead to the activation of numerous pro-inflammatory cytokine genes (IL-1, IL-6, TNF-α) which are involved in promotion of IR. this chain reaction will reduce insulin sensitivity and increase liver injury. Hepatic and peripheral IR along with altered lipogenesis will contribute in NAFLD progression. Hepatic IR will cause an increase expression of element-binding protein-1c (SREBP-1c). Increase of SREBP-1c will have an effect down stream which will cause inhibition of carnitine palmitoyl transferase-1 (CPT-1). CPT-1 inhibition will result in decreased oxidation of fatty acids increasing the amount of FFAs in the liver. When there is too much fatty acids stored in the body, it will ultimately lead to obesity.
Primary carnitine deficiency
Due to a mutation in the DNA, there is reduced amount of carnitine in the tissue, due to the carnitine being discharged in the urine. Similar to NAFLD, this causes the body to loss the ability to utilize fat and causing a build up of fat in the body. When there is excess fat stored in the body, it will lead to obesity.
Increased visceral (around organs) adiposity and insulin resistance (IR).Insulin resistance in the liver is associated with more hepatic glucose output due to insulin-suppressing effects on gluconeogenesis being impaired. Worsening hyperglycemia, resulting to type 2 diabetes. Peripheral IR (adipose tissue, skeletal muscle) causes increased free fatty acids (FFA) which move to the liver increased hepatic fatty acid synthesis and FFAs results in increased triglyceride accumulation in the liver. FFA re-esterification process causes long-chain acyl-CoAs and diacylglycerol (DAG) to accumulate. Excess FFAs prevents kinase interaction with phosphatidylinositol 3-kinase (PI3K) activation. The FFA-induced down-regulation of insulin signaling pathways results in several kinases involved in stress response being activated. Which will lead to the activation of numerous pro-inflammatory cytokine genes (IL-1, IL-6, TNF-α) which are involved in promotion of IR. this chain reaction will reduce insulin sensitivity and increase liver injury. Hepatic and peripheral IR along with altered lipogenesis will contribute in NAFLD progression. Hepatic IR will cause an increase expression of element-binding protein-1c (SREBP-1c). Increase of SREBP-1c will have an effect down stream which will cause inhibition of carnitine palmitoyl transferase-1 (CPT-1). CPT-1 inhibition will result in decreased oxidation of fatty acids increasing the amount of FFAs in the liver. When there is too much fatty acids stored in the body, it will ultimately lead to obesity.
Primary carnitine deficiency
Due to a mutation in the DNA, there is reduced amount of carnitine in the tissue, due to the carnitine being discharged in the urine. Similar to NAFLD, this causes the body to loss the ability to utilize fat and causing a build up of fat in the body. When there is excess fat stored in the body, it will lead to obesity.
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