Endocrine Abstracts

Introduction and aim: Obesity is a public health problem characterized by metabolic and endocrine disorders. Currently, it has been observed an increase of the obesity induced by high fat diet (HFD) and, considering that small intestine is the most important absorptive site of the nutrients, it is very interesting to evaluate the impact of HFD intake on that first place of nutrients entry, that is, the small intestine. Taken into account that dyslipidemia and hypertension are obesity common findings, we attempted to evaluate whether HFD consumption affects the microsomal triglyceride transfer protein (MTTP) and NHE3, since they promote triglyceride and sodium absorption, respectively. Considering that nutrients absorption could contribute to body weight gain and obesity, we also evaluated the nutrients transporters: SGLT1, GLUT2 and GLUT5 for carbohydrates, PEPT1 for peptides, FATP4, CD36/SR-B2 and NPC1L1 for long-chain fatty acids and cholesterol, respectively.

Methods: C57bl/6 male mice were fed standard diet (LFD) or HFD for three, six, nine or twelve weeks. At the end of each time, mice were killed and small intestine was removed and opened to detach the absorptive epithelium from mucosa. The epithelium was homogenate in appropriate lysis buffer and submitted to Western blotting (WB) technique for MTTP, NHE3, SGLT1, GLUT2, GLUT5, PEPT1, FATP4, CD36/SR-B2 and NPC1L1. PKA and PKC activities were analyzed by ELISA.

Results: HFD consumption from third up to 12^th week increased MTTP and NHE3 content, but decreased the GLUT2, PEPT1 and NPC1L1. HFD also decreased the CD36/SR-B2 content, but only from 9^th up to 12^th week. HFD did not affect the SGLT1, GLUT5 and FATP4 content at any time-course studied. HFD also decreased PKA and PKC activities at 12^th week.

Conclusion: Considering that mice began to gain weight from the third week after HFD consumption, the reduction of GLUT2, PEPT1 and NPC1L1 might interpose to the nutrients uptake, which could constitute a counter-regulation mechanism to limit the gain weight and adiposity. That condition could be reinforced by the decreased CD36/SR-B2 content observed from ninth week of HFD. Regarding the increase of MTTP and NHE3, we could infer that MTTP contributes to dyslipidemia and NHE3 contributes to hypertension both observed in the obesity and that constitutes the risk factors for cardiovascular diseases. Besides, all of these alterations might be linked to the reduction of PKA and PCK activities, at least for the NHE3, whose activity is known to be decreased by PKA.