Other Abstract | Objective
To evaluate the characteristics and mechanisms of hepatic glucose and fatty acid (FA) metabolism in rats during high altitude (HA) acclimatization at 4300m.
Methods
36 male SD rats were randomly assigned into six groups respectively named H1, H3, H7, H15 and H30 (HA exposure for 1 day, 3, 7, 15 and 30 days, respectively), and C (no HA exposure, controls). Plasma was collected to exam the content of FFA, lactate, blood glucose and ALT. The liver tissues were collected for the measurement of the mRNA and protein levels of seven factors involved in hepatic glucose and FA metabolism (ICDH, G6Pase, AMPK, FoxO1, CPT-I, PPARα and ACC-1), as well as the hepatic content of lactate, ATP, glycogen and total ketone body.
Results
We observed no significant difference in the blood levels of ALT, FFA, lactate and glucose as well as in the hepatic lactate content between the rats exposed to an altitude of 4,300m and those in control. Acute exposure of rats to HA was found to significantly alter the hepatic expressions of the following factors involved in glucose metabolism and FA metabolism: (1) increased levels of ICDH, G6Pase, glycogen (H1, H3, and H7) and reduced ATP content (H1); (2) decreased levels of AMPK and FoxO1 throughout the whole experimental period; (3) increased levels of CPT-I and PPARα, as well as increased production of hepatic total ketone body (H3); and (4) increased ACC-1 level (H1 and H3). Longer exposure (>15 days) caused a marked decrease in the levels of CPT-I and PPARα.
Conclusions
Increased hepatic gluconeogenesis, glycogen synthesis, ketogenesis, FA oxidation and synthesis in the early phase of HA exposure may be among the important mechanisms for the rats to acclimatize themselves to the stressful environments. FoxO1, PPARα and AMPK were involved in the regulation of hepatic glucose and FA metabolism. |