Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet

Abstract

Western diet is characterized by a hypercaloric and hyperlipidic intake, enriched in saturated fats, that is associated with the increased occurrence of metabolic diseases. To cope with this overload of dietary lipids, the intestine, which delivers dietary lipids to the body, has to adapt its capacity in lipid absorption and lipoprotein synthesis. We have studied the early effects of a high-fat diet (HFD) on intestinal lipid metabolism in mice. After 7 days of HFD, mice displayed normal fasting triglyceridemia but postprandial hypertriglyceridemia. HFD induced a decreased number of secreted chylomicrons with increased associated triglycerides. Secretion of larger chylomicrons was correlated with increased intestinal microsomal triglyceride transfer protein (MTP) content and activity. Seven days of HFD induced a repression of genes involved in fatty acid synthesis (FAS, ACC) and an increased expression of genes involved in lipoprotein assembly (apoB, MTP, and apoA-IV), suggesting a coordinated control of intestinal lipid metabolism to manage a high-fat loading. Of note, the mature form of the transcription factor SREBP-1c was increased and translocated to the nucleus, suggesting that it could be involved in the coordinated control of gene transcription. Activation of SREBP-1c was partly independent of LXR. Moreover, HFD induced hepatic insulin resistance whereas intestine remained insulin sensitive. Altogether, these results demonstrate that a short-term HFD is sufficient to impact intestinal lipid metabolism, which might participate in the development of dyslipidemia and metabolic diseases.

Brain Control of Plasma Cholesterol Involves Polysialic Acid Molecules in the Hypothalamus

“…These results support the existence of homeostatic mechanisms that limit the rise of VLDL-cholesterol during acute overfeeding and that maintain a balanced plasma lipoproteins profile. Our findings are in line with previous works that evidenced early adaptation of cholesterol metabolism during short-term HFD, and they further show that such mechanism occurs more rapidly than previously anticipated (Srivastava et al, 1991; Hernández Vallejo et al, 2009; Kahle et al, 2013). …”

“…Short-term HFD is also known to induce gene expression reprogramming in the liver affecting several enzymes and transporters involved in the lipoprotein metabolism. For instance, coordinated down-regulation of Acc, Fas , and Hmgcr , occurs in mouse liver after 1-week HFD, suggesting a reduction of VLDL synthesis on HFD (de Fourmestraux et al, 2004; Hernández Vallejo et al, 2009). These molecular data are consistent with a drop in VLDL release seen in this study.…”

“…Such homeostatic response likely results from complementary mechanisms taking place in various organs or tissues. Indeed, 1-week HFD is sufficient to change postprandial release, composition and size of chylomicrons by modulating intestinal lipid metabolism (Hernández Vallejo et al, 2009). Early transcriptional regulation of fatty acid metabolism-related enzymes has been observed in jejunum and duodenum upon 3-day HFD, indicating that the intestine is highly reactive to dietary fat (Clara et al, 2016).…”

High-Fat Diet Enhances Villus Growth During the Adaptation Response to Massive Proximal Small Bowel Resection

“…A previous study had shown that the gene expression of ApoB and MTTP, both involved in lipoprotein synthesis, were elevated in mice who were given a high-fat diet for 7 days. 15 Similarly, our study showed that ApoB mRNA expression increased in the setting of HFD regardless of operation. However, MTTP mRNA expression is elevated only in the SBR/HFD group with a relative increase of roughly twofold.…”

Pivotal role of inflammation in vascular endothelial dysfunction of hyperlipidemic rabbit and effects by atorvastatin

“…Some studies also demonstrated that not only long-term but also short-term high-fat diet would induce insulin resistance, cardiac dysfunction and even cause the increased risk of cardiac events [20][21][22][23]. However, the underlying mechanisms for the phenomena mentioned above are still unclear.…”