Suppression of circadian secretion of glucagon-like peptide-1 by the saturated fatty acid, palmitate.

AIM: Glucagon-like peptide-1 is an incretin hormone secreted by the intestinal L-cell with a circadian rhythm that parallels expression of the core clock gene, Bmal1. Although feeding rats a high-fat/high-sucrose Western diet impairs rhythmic glucagon-like peptide-1 release, the mechanisms underlying this effect remain unclear. Therefore, the aim of this study was to determine the pathway(s) by which the saturated fat, palmitate, a major component of the Western diet, impairs circadian glucagon-like peptide-1 secretion. METHODS: Murine mGLUTag L-cells were synchronized, and the effects of palmitate pre-treatment on gene expression and glucagon-like peptide-1 secretion were determined, in addition to metabolite quantification, mitochondrial function analysis and enzyme inhibition and activation assays. Glucagon-like peptide-1 secretion was also analysed in ileal crypt cultures from control and Bmal1 knockout mice. RESULTS: Pre-treatment with palmitate dampened Bmal1 mRNA and protein expression and glucagon-like peptide-1 secretion at 8 but not 20 hours after cell synchronization (P < .05-.001). Glucagon-like peptide-1 release was also impaired in Bmal1 knockout cultures as compared to wild-type controls (P < .001). Palmitate pre-treatment reduced expression of the Bmal1 downstream target, nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the synthesis of NAD+ . This was paralleled by dampening of total NAD+ levels, as well as impaired mitochondrial function and ATP production (P < .05-.001). Whereas direct inhibition of nicotinamide phosphoribosyltransferase also decreased glucagon-like peptide-1 release, activation of this enzyme restored glucagon-like peptide-1 secretion in the presence of palmitate. CONCLUSION: Palmitate impairs L-cell clock function at the peak of Bmal1 gene expression, thereby impairing mitochondrial function and ultimately rhythmic glucagon-like peptide-1 secretion.

[The image of intravertebral somatic gaseous dissection. Report of 9 cases one of which has a triple localization and review of the literature]. / L'image de dissection gazeuse somatique intravertébrale. A propos de 9 observations dont une forme à triple localisation et revue de la littérature.

We report a series of 9 cases of vertebral somatic gaseous dissection studied between 1978 and 1989. We find most of the characteristics established from the literature data: advanced age, possible medullar compression contrary to the vertebral compression by common osteoporosis, predilection for the dorso-lumbar junction, frequency of the osteoporosis, possibility of metabolic disorders, of occurrence after radiotherapy. The context of the occurrence and the paraclinical examinations of the whole have enabled us to eliminate, in this series, a malignant pathology. However, when there exists a doubt on a malignant origin, it is preferable to carry out a vertebral biopsy with a trocar. In fact, the image may not be pathognomonic of a benign vertebral osteoporosis. Finally, we give the first description of a triple localization of vertebral gaseous dissection.