INVESTIGADORES
CASTRO Maria Cecilia
congresos y reuniones científicas
Título:
OXIDATIVE STRESS MEDIATES METABOLIC AND ENDOCRINE DYSFUNCTIONS INDUCED BY FRUCTOSE
Autor/es:
CASTRO MC; FRANCINI F; SCHINELLA G; GONZÁLEZ ARBELAEZ LF; GAGLIARDINO JJ; MASSA ML
Lugar:
Cancun
Reunión:
Congreso; XXIII Congreso de la Asociación Latinoamericana para el Estudio del Hígado; 2014
Resumen:
Introduction: The prevalence of
Type 2 Diabetes Mellitus is increasing worldwide, normally associated
to other risk factors: hypertension, obesity, unhealthy diets and
sedentary lifestyle. Recent publications suggested that the increase in
fructose consume registered in the last decades has contributed to the
current obesity and diabetes epidemics. Administration of a fructose
rich diet (FRD) to normal rats mimics this situation.
Objective:
to evaluate in a model of pre-diabetes the possible preventive effect
of the antioxidant lipoic acid (LA) on the insulin-resistance (IR),
liver steatosis, metabolic dysfunctions, oxidative stress (OS) and
inflammation triggered by a FRD.
Material
& Methods: Wistar rats were fed during 21 days a commercial diet
and tap water (control [C]) or fructose in the drinking water 10% (F)
and C and F plus LA (35 mg/kg body weight/day, i.p. during the last 5
days of the treatment) (CL and FL). After that, animals were sacrificed
and measured glycemia (GOD-PAP), triglyceridemia (TG) (colorimetric)
and insulinemia (RIA). Glucose tolerance test was also performed. In the
liver we measured a) OS markers (GSH and carbonyls in proteins) and
enzymes of the antioxidant defense system (SOD1, SOD2 and catalase), b)
liver steatosis (Oil-Red), c) gene expression of lipogenic enzymes and
the related transcription factor (GPAT, FAS, CPT-1, SREBP-1c), d)
glucokinase, fructokinase, G-6-Pase and G-6-PDH activities, e)
expression of IL-1B, TNFalfa and COX2 and f) insulin signaling pathway
mediators (IR, IRS1/2, PI3K).
Results:
Three weeks of a FRD induced: a) hypertriglyceridemia,
hyperinsulinemia and impaired glucose tolerance, b) hepatic OS (increase
in OS markers, reduction in the expression of antioxidant enzymes and
enhanced p22phox and gp91phox levels ?NADPH
oxidase-), c) liver steatosis related to increased FAS and GPAT
expression as well as SREBP-1c and decreased in CPT-1 expression, d)
enhanced fructokinase, G-6-Pase and G-6-PDH activities and glycogen
content, e) increased glucokinase activity related to translocation to
the cytosol and enhanced expression of its positive regulator in the
same compartment, e) increased in liver inflammatory markers and f)
alteration in the insulin signaling pathway. These disturbances were
prevented by LA administration.
Conclusion:
OS could play a pivotal role in the development of the endocrine and
metabolic alterations induced by a FRD. The protective effect on the
liver glucose sensor (glucokinase) could be partially adscript to a
re-localization of the enzyme in the nucleus and the cytosolic
regulation by PFK-2. Interestingly LA seems to have also a corrective
effect on cytosolic NADPH oxidase expression.