Time sequence of the intensification of the liver glucose production induced by high-fat diet in mice.
It is well established that the development of insulin resistance shows a temporal sequence in different organs and tissues. Moreover, considering that the main aspect of insulin resistance in liver is a process of glucose overproduction from gluconeogenesis, we investigated if this metabolic change also shows temporal sequence. For this purpose, a well-established experimental model of insulin resistance induced by high-fat diet (HFD) was used. The mice received HFD (HFD group) or standard diet (COG group) for 1, 7, 14 or 56 days. The HFD group showed increased (P < 0.05 versus COG) epididymal, retroperitoneal and inguinal fat weight from days 1 to 56. In agreement with these results, the HFD group also showed higher body weight (P < 0.05 versus COG) from days 7 to 56. Moreover, the changes induced by HFD on liver gluconeogenesis were progressive because the increment (P < 0.05 versus COG) in glucose production from l-lactate, glycerol, l-alanine and l-glutamine occurred 7, 14, 56 and 56 days after the introduction of the HFD schedule, respectively. Furthermore, glycaemia and cholesterolemia increased (P < 0.05 versus COG) 14 days after starting the HFD schedule. Taken together, the results suggest that the intensification of liver gluconeogenesis induced by an HFD is not a synchronous 'all-or-nothing process' but is specific for each gluconeogenic substrate and is integrated in a temporal manner with the progressive augmentation of fasting glycaemia.
Department of Pharmacology and Therapeutic, State University of Maringá, Maringá, Paraná State, PR, 87020-900, Brazil.
Simoni
S
Obici
Thauany Martins
TM
Tavoni
Helenton C
HC
Barrena
Rui
R
Curi
Roberto B
RB
Bazotte
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D014280:Triglycerides; D002784:Cholesterol; D005947:Glucose