scholarly journals Cell-Type–Specific, Ketohexokinase-Dependent Induction by Fructose of Lipogenic Gene Expression in Mouse Small Intestine

2020 ◽  
Vol 150 (7) ◽  
pp. 1722-1730 ◽  
Author(s):  
Arwa Al-Jawadi ◽  
Chirag R Patel ◽  
Reilly J Shiarella ◽  
Emmanuellie Romelus ◽  
Madelyn Auvinen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Metabolic Diseases ◽  
Free Access ◽  
Wild Type ◽  
Cell Type ◽  
Lipogenic Gene ◽  
Lipogenic Genes ◽  
Lipogenic Gene Expression ◽  
Small Intestinal

ABSTRACT Background High intakes of fructose are associated with metabolic diseases, including hypertriglyceridemia and intestinal tumor growth. Although small intestinal epithelia consist of many different cell types, express lipogenic genes, and convert dietary fructose to fatty acids, there is no information on the identity of the cell type(s) mediating this conversion and on the effects of fructose on lipogenic gene expression. Objectives We hypothesized that fructose regulates the intestinal expression of genes involved in lipid and apolipoprotein synthesis, that regulation depends on the fructose transporter solute carrier family 2 member a5 [Slc2a5 (glucose transporter 5)] and on ketohexokinase (Khk), and that regulation occurs only in enterocytes. Methods We compared lipogenic gene expression among different organs from wild-type adult male C57BL mice consuming a standard vivarium nonpurified diet. We then gavaged twice daily for 2.5 d fructose or glucose solutions (15%, 0.3 mL per mouse) into wild-type, Slc2a5-knockout (KO), and Khk-KO mice with free access to the nonpurified diet and determined expression of representative lipogenic genes. Finally, from mice fed the nonpurified diet, we made organoids highly enriched in enterocyte, goblet, Paneth, or stem cells and then incubated them overnight in 10 mM fructose or glucose. Results Most lipogenic genes were significantly expressed in the intestine relative to the kidney, liver, lung, and skeletal muscle. In vivo expression of Srebf1, Acaca, Fasn, Scd1, Dgat1, Gk, Apoa4, and Apob mRNA and of Scd1 protein increased (P < 0.05) by 3- to 20-fold in wild-type, but not in Slc2a5-KO and Khk-KO, mice gavaged with fructose. In vitro, Slc2a5- and Khk-dependent, fructose-induced increases, which ranged from 1.5- to 4-fold (P < 0.05), in mRNA concentrations of all these genes were observed only in organoids enriched in enterocytes. Conclusions Fructose specifically stimulates expression of mouse small intestinal genes for lipid and apolipoprotein synthesis. Secretory and stem cells seem incapable of transport- and metabolism-dependent lipogenesis, occurring only in absorptive enterocytes.

scholarly journals ADD1/SREBP-1c Is Required in the Activation of Hepatic Lipogenic Gene Expression by Glucose

1999 ◽  
Vol 19 (5) ◽  
pp. 3760-3768 ◽  
Author(s):  
Marc Foretz ◽  
Corinne Pacot ◽  
Isabelle Dugail ◽  
Patricia Lemarchand ◽  
Colette Guichard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid Synthase ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Dominant Negative ◽  
Temporal Association ◽  
Lipogenic Gene ◽  
Lipogenic Genes ◽  
Lipogenic Gene Expression ◽  
Carbohydrate Feeding

ABSTRACT The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of l-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin.

scholarly journals Trans-10, cis-12 conjugated linoleic acid reduces milk fat content and lipogenic gene expression in the mammary gland of sows without altering litter performance

2019 ◽  
Vol 123 (6) ◽  
pp. 610-618 ◽  
Author(s):  
E. C. Sandri ◽  
K. J. Harvatine ◽  
D. E. Oliveira
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Milk Fat ◽  
Fat Content ◽  
Lipogenic Gene ◽  
Lipogenic Genes ◽  
Lipogenic Gene Expression

AbstractTrans-10, cis-12 conjugated linoleic acid (CLA) decreases milk fat synthesis in lactating sows and involves, at least in part, the down-regulation of lipogenic genes. The objective was to evaluate the effect of CLA on milk composition and lipogenic gene expression. Twenty multiparous sows were randomly assigned to one of the two treatments for 18 d (from day 7 to day 25 of lactation): (1) control (no CLA added) and (2) 1 % of CLA mixed into the ration. CLA treatment decreased milk fat and protein content by 20 % (P = 0·004) and 11 % (P = 0·0001), respectively. However, piglet weight did not differ between treatments (P = 0·60). Dietary CLA increased the concentration of SFA in milk fat by 16 % (P < 0·0001) and decreased MUFA by 17·6 % (P < 0·0001). In the mammary gland, CLA reduced gene expression of acetyl-CoA carboxylase-α by 37 % (P = 0·003), fatty acid synthase by 64 % (P = 0·002), stearoyl-CoA desaturase 1 by 52 % (P = 0·003), lipoprotein lipase by 26 % (P = 0·03), acyl glycerol phosphate acyltransferase 6 by 15 % (P = 0·02) and diacylglycerol acyltransferase 1 by 27 % (P = 0·02), whereas the expression of fatty acid binding protein 3 was not altered by CLA treatment (P = 0·09). Mammary expression of casein-β and α-lactalbumin was reduced by CLA by 68 % (P = 0·0004) and 62 % (P = 0·005), respectively. Additionally, CLA had no effect on the expression of lipogenic genes evaluated in adipose tissue. In summary, CLA reduced milk fat content without negatively affecting litter performance and it affected mammary expression of genes involved in all lipogenic pathways studied.

scholarly journals XBP1s Is an Anti-lipogenic Protein

2016 ◽  
Vol 291 (33) ◽  
pp. 17394-17404 ◽  
Author(s):  
Hilde Herrema ◽  
Yingjiang Zhou ◽  
Dongyan Zhang ◽  
Justin Lee ◽  
Mario Andres Salazar Hernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Transcription Factor ◽  
Fatty Liver ◽  
Er Stress ◽  
Metabolic Diseases ◽  
Synthesis Rate ◽  
Alcoholic Fatty Liver ◽  
Lipogenic Gene ◽  
Lipogenic Gene Expression

Endoplasmic reticulum (ER) stress has been shown to contribute to various metabolic diseases, including non-alcoholic fatty liver disease and type 2 diabetes. Reduction of ER stress by treatment with chemical chaperones or overexpression of ER chaperone proteins alleviates hepatic steatosis. Nonetheless, X-box binding protein 1s (XBP1s), a key transcription factor that reduces ER stress, has been proposed as a lipogenic transcription factor. In this report, we document that XBP1s leads to suppression of lipogenic gene expression and reduction of hepatic triglyceride and diacylglycerol content in livers of diet-induced obese and genetically obese and insulin-resistant ob/ob mice. Furthermore, we also show that PKCϵ activity, which correlates with fatty liver and which causes insulin resistance, was significantly reduced in diet-induced obese mice. Finally, we have shown that XBP1s reduces the hepatic fatty acid synthesis rate and enhances macrolipophagy, an initiating step in lipolysis. Our results reveal that XBP1s reduces hepatic lipogenic gene expression and improves hepatosteatosis in mouse models of obesity and insulin resistance, which leads us to conclude that XBP1s has anti-lipogenic properties in the liver.

scholarly journals mTORC1 Is Essential for Early Steps during Schwann Cell Differentiation of Amniotic Fluid Stem Cells and Regulates Lipogenic Gene Expression

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107004 ◽  
Author(s):  
Andrea Preitschopf ◽  
Kongzhao Li ◽  
David Schörghofer ◽  
Katharina Kinslechner ◽  
Birgit Schütz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Differentiation ◽  
Schwann Cell ◽  
Amniotic Fluid ◽  
Lipogenic Gene ◽  
Amniotic Fluid Stem Cells ◽  
Lipogenic Gene Expression ◽  
Schwann Cell Differentiation

scholarly journals Hepatic Glucokinase Is Required for the Synergistic Action of ChREBP and SREBP-1c on Glycolytic and Lipogenic Gene Expression

2004 ◽  
Vol 279 (19) ◽  
pp. 20314-20326 ◽  
Author(s):  
Renaud Dentin ◽  
Jean-Paul Pégorier ◽  
Fadila Benhamed ◽  
Fabienne Foufelle ◽  
Pascal Ferré ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Metabolism ◽  
Binding Protein ◽  
Synergistic Action ◽  
Glucose Effect ◽  
Lipogenic Gene ◽  
Lipogenic Genes ◽  
Lipogenic Gene Expression ◽  
Spot 14 ◽  
Element Binding Protein

Hepatic glucokinase (GK) catalyzes the phosphorylation of glucose to glucose 6-phosphate (G6P), a step which is essential for glucose metabolism in liver as well as for the induction of glycolytic and lipogenic genes. The sterol regulatory element-binding protein-1c (SREBP-1c) has emerged as a major mediator of insulin action on hepatic gene expression, but the extent to which its transcriptional effect is caused by an increased glucose metabolism remains unclear. Through the use of hepatic GK knockout mice (hGK-KO) we have shown that the acute stimulation by glucose ofl-pyruvate kinase (l-PK), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), andSpot 14genes requires GK expression. To determine whether the effect of SREBP-1c requires GK expression and subsequent glucose metabolism, a transcriptionally active form of SREBP-1c was overexpressed bothin vivoand in primary cultures of control and hGK-KO hepatocytes. Our results demonstrate that the synergistic action of SREBP-1c and glucose metabolism via GK is necessary for the maximal induction ofl-PK, ACC, FAS, andSpot 14gene expression. Indeed, in hGK-KO hepatocytes overexpressing SREBP-1c, the effect of glucose on glycolytic and lipogenic genes is lost because of the impaired ability of these hepatocytes to efficiently metabolize glucose, despite a marked increase in lowKmhexokinase activity. Our studies also reveal that the loss of glucose effect observed in hGK-KO hepatocytes is associated with a decreased in the carbohydrate responsive element-binding protein (ChREBP) gene expression, a transcription factor suggested to mediate glucose signaling in liver. DecreasedChREBPgene expression, achieved using small interfering RNA, results in a loss of glucose effect on endogenous glycolytic (l-PK) and lipogenic (FAS, ACC) gene expression, thereby demonstrating the direct implication of ChREBP in glucose action. Together these results support a model whereby both SREBP-1c and glucose metabolism, acting via ChREBP, are necessary for the dietary induction of glycolytic and lipogenic gene expression in liver.

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