Energy Metabolism in the Liver

Abstract

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD).

MicroRNAs: An adaptive mechanism in the pancreatic β-cell…and beyond?

“…The liver maintains a high regenerative capacity and maintains a central role in both glucose and lipid metabolism and it would be of great interest to determine whether the miRNA pathway is integral to balancing these processes in the hepatocyte [43]. In the steady state, proliferation rates are low, however it is unclear whether its function in gluconeogenesis, glycogen storage, and lipid oxidation are compromised as soon as the cell's demand for growth are increased [44]. The intestine is also known for its high capacity for glucose utilization and proliferation, however it is also unclear whether miRNAs play a role in this tissue to maintain the balance of these functions [45].…”

Depletion of suppressor of cytokine signaling-1a causes hepatic steatosis and insulin resistance in zebrafish

“…GH signaling is known to stimulate gluconeogenesis, lipolysis, and adipose tissue mobilization in mammals and teleosts (26,28,36). A central role of the JAK2-STAT5 pathway in mediating the growth-stimulating action of GH signaling has been reported in teleosts (23).…”

“…Energy metabolism and somatic growth are closely coordinated in animals, and the liver is a key metabolic organ that governs body energy metabolism (36). With an evident defect in somatic growth in the homozygous socs1a-deficient adult zebrafish (Fig.…”

“…4, A, C, and D). Because the liver is the major organ involved in lipid metabolism and homeostasis (36), the pathological features of the liver were examined by Oil Red O staining. Severe lipid accumulation and hepatic steatosis were observed in the liver of socs1a-deficient zebrafish (Fig.…”

Nuclear receptors and liver disease: Summary of the 2017 basic research symposium

“…These perturbations include obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance 4. PPARα is activated in the liver in the fasted state and has roles in coordinating fatty acid oxidation 5. In contrast, FXR is activated under the fed state by bile acids (BAs) to maintain BA homeostasis.…”