Virginie Lecomte - Academia.edu (original) (raw)
Papers by Virginie Lecomte
genes identify new regulatory pathways in muscle Microarray analyses of SREBP-1a and SREBP-1c tar... more genes identify new regulatory pathways in muscle Microarray analyses of SREBP-1a and SREBP-1c target You might find this additional info useful... 24 times a year (twice monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD systems with techniques linking genes and pathways to physiology, from prokaryotes to eukaryotes. It is published publishes results of a wide variety of studies from human and from informative model Physiological Genomics
Les proteines SREBP-1, Sterol Response Element Binding Proteins, sont des regulateurs cles du met... more Les proteines SREBP-1, Sterol Response Element Binding Proteins, sont des regulateurs cles du metabolisme des lipides et du cholesterol. A ce titre, ils ont ete largement etudies dans le foie et le tissu adipeux. Les facteurs SREBP-1 sont egalement exprimes dans le muscle squelettique au sein duquel ils sont les principaux mediateurs des effets geniques de l’insuline.Les travaux de these presentes dans ce manuscrit ont eu pour but de definir le role specifique de SREBP-1 dans le muscle squelettique. L’etude transcriptomique de cellules musculaires humaines revele plus de1500 genes regules par SREBP-1 dans le muscle squelettique humain, dont la moitie est reprimee. L’analyse fonctionnelle de ces genes revele l’implication de SREBP-1 dans des fonctions musculaires depassant la cadre du metabolisme glucido-lipidique. Ainsi, SREBP-1 inhibe l’expression de plusieurs genes impliques dans la differenciation et le maintien du phenotype musculaire. En consequence, la sur expression de SREBP-...
Cells, 2021
Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Her... more Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of...
Current Developments in Nutrition
Objectives Emerging evidence suggests that paternal obesity plays a significant role on offspring... more Objectives Emerging evidence suggests that paternal obesity plays a significant role on offspring health. Our previous work in rodents showed that high fat diet (HFD) induced paternal obesity reduced offspring glucose tolerance. It has also been reported that paternal obesity can initiate metabolic disturbance in subsequent generations. Therefore, we designed a novel micronutrient supplement to ameliorate the transgenerational effects of paternal obesity. Methods Founder (F0) male Sprague Dawley rats (3 weeks, 12 per group) were weaned on control (CD) or HFD or diets containing micronutrient supplement (CS; HS), after which they were mated with CD fed females at 19 weeks of age. Twelve F1 offspring from each litter across the four diet groups were weaned on day 21 onto CD, generating four F1 groups. After 14 weeks on CD, they were mated with CD fed females. Male F2 siblings were fed CD or HFD from day 21. After 6 weeks on diet, they underwent EchoMRI (See attached study design). Res...
Current Developments in Nutrition
Objectives Growing evidence shows detrimental effects of paternal obesity on subsequent generatio... more Objectives Growing evidence shows detrimental effects of paternal obesity on subsequent generations. We designed a micronutrient supplement whose components participate in one carbon metabolism and are anticipated to improve antioxidant capacity. Here, we studied the effects of the supplement on metabolic health and hepatic lipid metabolism in male rats consuming either a normal healthy diet or an obesogenic diet. Methods Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (CD) or high fat diet (HFD) with or without added micronutrient supplement (CDS; HFDS). After 12 weeks of diet, body composition was measured by magnetic resonance imaging, and blood samples were collected to assess supplementation levels. After 19 weeks of diet, oral glucose tolerance test (OGTT) was performed and plasma was collected to determine insulin release. At 27 weeks of diet, the rats were fasted and culled to harvest blood and tissues. Liver lipids and expression of genes involved ...
American journal of physiology. Endocrinology and metabolism, Feb 1, 2017
Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our... more Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skelet...
Scientific reports, Mar 31, 2017
Unhealthy diets, and ensuing weight gain, predispose individuals to the development of esophageal... more Unhealthy diets, and ensuing weight gain, predispose individuals to the development of esophageal adenocarcinoma. We examined the effect of chronic high fat diet (HFD) on the esophageal microbiota of Sprague Dawley rats using Illumina MiSeq amplicon sequencing (V4, 515 F/806 R) and on esophageal expression of IL18, PTGS2, PPARA, FFAR3, and CRAT. The relationships among metabolic parameters, esophageal microbiota, and host gene expression were determined. We observed a significant difference between the upper and lower esophageal microbiota in control fed rats, emphasized by enrichment of Lactobacillus species in the lower esophagus. Rats on HFD gained significantly more fat and had reduced insulin sensitivity. Diet type significantly affected the esophageal microbiota, with Clostridium sensu stricto being enriched in both upper and lower segments of HFD fed rats. Of interest, bacterial pathways related to carotenoid biosynthesis were significantly decreased in the lower esophagus of...
Aim: While the impact of maternal obesity on offspring metabolism is well documented, strong evid... more Aim: While the impact of maternal obesity on offspring metabolism is well documented, strong evidence for a paternal obesity influence are just emerging. Our lab recently showed that female rat offspring from high fat diet (HFD) fed fathers developed glucose intolerance and defective insulin secretion (SF Ng, Nature, 2010). This demonstrated that metabolic defects from the father can be passed on to the F1 generation. Here we extend this work to study the risk of metabolic syndrome transmission through the paternal line to the F2 generation. Methods: F0 male rats were fed a HFD or control diet (CD) from 3 weeks of age for 13 weeks before being mated with control females. The F1 male offspring were weaned on CD then mated at 14 weeks with control females. F2 male and female offspring were fed either CD or HFD after weaning until 27 weeks of age. Results: When fed a CD, the metabolic phenotype of F2 from a HFD F0 grandfather did not differ from those from a Control F0. But when fed a ...
DOHaD13-1640- The number of obese and overweight adults has reached pandemic proportions. There i... more DOHaD13-1640- The number of obese and overweight adults has reached pandemic proportions. There is clear evidence that perturbation of the maternal environment can impact the offspring’s development and predispose them to metabolic disease in adult life. This may explain the relatively sudden increase in adults at risk of metabolic disease. Until recently the paternal contribution to the programming of metabolic disease has been thought to be minimal. Our group was one of the first to demonstrate that paternal obesity also confers metabolic changes to the offspring (Ng et al, 2010) at 6 and 12 weeks of age. As the study by Ng et al, 2010 focused on females, the current study investigated metabolic alterations in adult male offspring. The male phenotype appears to be clearly different from that described in the females by Ng et al. 2010. F1 Male offspring from HFD fed fathers in this new study displayed mild intra-uterine growth restriction; early catch up growth followed by an earli...
Asian Journal of Andrology, 2015
methylation state of regulatory regions in spermatozoa (and oocytes) controls gene transcription ... more methylation state of regulatory regions in spermatozoa (and oocytes) controls gene transcription in offspring. 7 Like many other cell types, mature spermatozoa in humans and rodents have high methylation levels at most repetitive elements and intergenic regions that transcriptionally repress these regions. Gene-specific hyper-or hypo-methylation is found at promoters, with a general observation of decreasing methylation with increasing CpG density. 8-12 Furthermore, the promoters of genes involved in early development are more likely to be hypo-methylated, suggesting that they are primed for activation in offspring. 10,12 Several studies have described alteration of normal sperm DNA methylation patterns, due to genotype, environmental exposure or disease. These include methylation changes associated with mutations in DNA methyltransferases, 13 reduced fertility, 14-17 toxin and drug exposure, 18-20 dietary alterations, 21,22 and stress exposure. 23,24 There is no sign of a "standard epigenetic response" to these insults, as increases and decreases in global and locus-specific DNA methylation have all been reported. An obstacle to the persistence of sperm methylation states in offspring is the extensive demethylation of the paternally-inherited chromosomes after fertilisation in humans and rodents. 25,26 Therefore,
Obesity Research & Clinical Practice, 2014
ABSTRACT Transgenerational inheritance of metabolic disease may be a strong contributor to the gl... more ABSTRACT Transgenerational inheritance of metabolic disease may be a strong contributor to the global obesity epidemic. While the impact of maternal obesity on offspring metabolism is well documented, strong evidence for an influence of paternal obesity is just emerging. Our group was one of the first to demonstrate that paternal obesity confers metabolic changes to the female offspring (Ng et al., 2010). Here we show that the male offspring are also impacted by their father's metabolic status. Sprague-Dawley rat fathers were fed either a control diet (CD-F0) or a high fat diet (HFD-F0) for 14 weeks before being mated with control females. The male offspring were weaned onto a control diet and killed either at 8 weeks or 6 months of age. Five weeks after weaning, the males from HFD-F0 showed a slow down in growth resulting in a significantly lower body weight from 9 weeks to 6 months of age. A decrease in plasma level of growth hormone and IGF1 was detected in 8 week old rats from HFD-F0. These rats presented smaller fat pads with a decrease in expression of Pparg and Igf1r in retro-peritoneal fat. In parallel, a decrease in expression of genes involved in muscle growth (Ghr, Igf1, mTOR and MyoD) was observed in tibialis anterioris muscle of males from HFD-F0. This resulted in smaller animals at 6 months of age that had smaller fat pads and muscles. The muscles of these rats showed ectopic lipid deposition with an increased expression of genes driving lipogenesis (Srebf1 and Fasn). The changes in growth and metabolism appeared to have no impact on glucose tolerance of 6 months old offspring. As observed in other models of programming (e.g. maternal low protein diet), investigating later stages of adulthood may uncover more direct metabolic consequences indicative of disease.
Physiological genomics, Jan 15, 2008
In this study we have identified the target genes of sterol regulatory element binding protein (S... more In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modified the mRNA level of 514 genes (310 upregulated and 204 downregulated). Gene ontology analysis indicated that in human muscle cells SREBP-1a and -1c are involved in the regulation of a large number of genes that are at the crossroads of different functional pathways, several of which are not directly connected with cholesterol and lipid metabolism. Six hundred fifty-two of all genes identified to be differentially regulated on SREBP overexpression had a sterol regulatory element (SRE) motif in their promoter sequences....
Obesity Research & Clinical Practice, 2013
Molecular and Cellular Biology, 2010
The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and... more The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.
Diabetes & Metabolism, 2008
genes identify new regulatory pathways in muscle Microarray analyses of SREBP-1a and SREBP-1c tar... more genes identify new regulatory pathways in muscle Microarray analyses of SREBP-1a and SREBP-1c target You might find this additional info useful... 24 times a year (twice monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD systems with techniques linking genes and pathways to physiology, from prokaryotes to eukaryotes. It is published publishes results of a wide variety of studies from human and from informative model Physiological Genomics
Les proteines SREBP-1, Sterol Response Element Binding Proteins, sont des regulateurs cles du met... more Les proteines SREBP-1, Sterol Response Element Binding Proteins, sont des regulateurs cles du metabolisme des lipides et du cholesterol. A ce titre, ils ont ete largement etudies dans le foie et le tissu adipeux. Les facteurs SREBP-1 sont egalement exprimes dans le muscle squelettique au sein duquel ils sont les principaux mediateurs des effets geniques de l’insuline.Les travaux de these presentes dans ce manuscrit ont eu pour but de definir le role specifique de SREBP-1 dans le muscle squelettique. L’etude transcriptomique de cellules musculaires humaines revele plus de1500 genes regules par SREBP-1 dans le muscle squelettique humain, dont la moitie est reprimee. L’analyse fonctionnelle de ces genes revele l’implication de SREBP-1 dans des fonctions musculaires depassant la cadre du metabolisme glucido-lipidique. Ainsi, SREBP-1 inhibe l’expression de plusieurs genes impliques dans la differenciation et le maintien du phenotype musculaire. En consequence, la sur expression de SREBP-...
Cells, 2021
Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Her... more Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of...
Current Developments in Nutrition
Objectives Emerging evidence suggests that paternal obesity plays a significant role on offspring... more Objectives Emerging evidence suggests that paternal obesity plays a significant role on offspring health. Our previous work in rodents showed that high fat diet (HFD) induced paternal obesity reduced offspring glucose tolerance. It has also been reported that paternal obesity can initiate metabolic disturbance in subsequent generations. Therefore, we designed a novel micronutrient supplement to ameliorate the transgenerational effects of paternal obesity. Methods Founder (F0) male Sprague Dawley rats (3 weeks, 12 per group) were weaned on control (CD) or HFD or diets containing micronutrient supplement (CS; HS), after which they were mated with CD fed females at 19 weeks of age. Twelve F1 offspring from each litter across the four diet groups were weaned on day 21 onto CD, generating four F1 groups. After 14 weeks on CD, they were mated with CD fed females. Male F2 siblings were fed CD or HFD from day 21. After 6 weeks on diet, they underwent EchoMRI (See attached study design). Res...
Current Developments in Nutrition
Objectives Growing evidence shows detrimental effects of paternal obesity on subsequent generatio... more Objectives Growing evidence shows detrimental effects of paternal obesity on subsequent generations. We designed a micronutrient supplement whose components participate in one carbon metabolism and are anticipated to improve antioxidant capacity. Here, we studied the effects of the supplement on metabolic health and hepatic lipid metabolism in male rats consuming either a normal healthy diet or an obesogenic diet. Methods Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (CD) or high fat diet (HFD) with or without added micronutrient supplement (CDS; HFDS). After 12 weeks of diet, body composition was measured by magnetic resonance imaging, and blood samples were collected to assess supplementation levels. After 19 weeks of diet, oral glucose tolerance test (OGTT) was performed and plasma was collected to determine insulin release. At 27 weeks of diet, the rats were fasted and culled to harvest blood and tissues. Liver lipids and expression of genes involved ...
American journal of physiology. Endocrinology and metabolism, Feb 1, 2017
Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our... more Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skelet...
Scientific reports, Mar 31, 2017
Unhealthy diets, and ensuing weight gain, predispose individuals to the development of esophageal... more Unhealthy diets, and ensuing weight gain, predispose individuals to the development of esophageal adenocarcinoma. We examined the effect of chronic high fat diet (HFD) on the esophageal microbiota of Sprague Dawley rats using Illumina MiSeq amplicon sequencing (V4, 515 F/806 R) and on esophageal expression of IL18, PTGS2, PPARA, FFAR3, and CRAT. The relationships among metabolic parameters, esophageal microbiota, and host gene expression were determined. We observed a significant difference between the upper and lower esophageal microbiota in control fed rats, emphasized by enrichment of Lactobacillus species in the lower esophagus. Rats on HFD gained significantly more fat and had reduced insulin sensitivity. Diet type significantly affected the esophageal microbiota, with Clostridium sensu stricto being enriched in both upper and lower segments of HFD fed rats. Of interest, bacterial pathways related to carotenoid biosynthesis were significantly decreased in the lower esophagus of...
Aim: While the impact of maternal obesity on offspring metabolism is well documented, strong evid... more Aim: While the impact of maternal obesity on offspring metabolism is well documented, strong evidence for a paternal obesity influence are just emerging. Our lab recently showed that female rat offspring from high fat diet (HFD) fed fathers developed glucose intolerance and defective insulin secretion (SF Ng, Nature, 2010). This demonstrated that metabolic defects from the father can be passed on to the F1 generation. Here we extend this work to study the risk of metabolic syndrome transmission through the paternal line to the F2 generation. Methods: F0 male rats were fed a HFD or control diet (CD) from 3 weeks of age for 13 weeks before being mated with control females. The F1 male offspring were weaned on CD then mated at 14 weeks with control females. F2 male and female offspring were fed either CD or HFD after weaning until 27 weeks of age. Results: When fed a CD, the metabolic phenotype of F2 from a HFD F0 grandfather did not differ from those from a Control F0. But when fed a ...
DOHaD13-1640- The number of obese and overweight adults has reached pandemic proportions. There i... more DOHaD13-1640- The number of obese and overweight adults has reached pandemic proportions. There is clear evidence that perturbation of the maternal environment can impact the offspring’s development and predispose them to metabolic disease in adult life. This may explain the relatively sudden increase in adults at risk of metabolic disease. Until recently the paternal contribution to the programming of metabolic disease has been thought to be minimal. Our group was one of the first to demonstrate that paternal obesity also confers metabolic changes to the offspring (Ng et al, 2010) at 6 and 12 weeks of age. As the study by Ng et al, 2010 focused on females, the current study investigated metabolic alterations in adult male offspring. The male phenotype appears to be clearly different from that described in the females by Ng et al. 2010. F1 Male offspring from HFD fed fathers in this new study displayed mild intra-uterine growth restriction; early catch up growth followed by an earli...
Asian Journal of Andrology, 2015
methylation state of regulatory regions in spermatozoa (and oocytes) controls gene transcription ... more methylation state of regulatory regions in spermatozoa (and oocytes) controls gene transcription in offspring. 7 Like many other cell types, mature spermatozoa in humans and rodents have high methylation levels at most repetitive elements and intergenic regions that transcriptionally repress these regions. Gene-specific hyper-or hypo-methylation is found at promoters, with a general observation of decreasing methylation with increasing CpG density. 8-12 Furthermore, the promoters of genes involved in early development are more likely to be hypo-methylated, suggesting that they are primed for activation in offspring. 10,12 Several studies have described alteration of normal sperm DNA methylation patterns, due to genotype, environmental exposure or disease. These include methylation changes associated with mutations in DNA methyltransferases, 13 reduced fertility, 14-17 toxin and drug exposure, 18-20 dietary alterations, 21,22 and stress exposure. 23,24 There is no sign of a "standard epigenetic response" to these insults, as increases and decreases in global and locus-specific DNA methylation have all been reported. An obstacle to the persistence of sperm methylation states in offspring is the extensive demethylation of the paternally-inherited chromosomes after fertilisation in humans and rodents. 25,26 Therefore,
Obesity Research & Clinical Practice, 2014
ABSTRACT Transgenerational inheritance of metabolic disease may be a strong contributor to the gl... more ABSTRACT Transgenerational inheritance of metabolic disease may be a strong contributor to the global obesity epidemic. While the impact of maternal obesity on offspring metabolism is well documented, strong evidence for an influence of paternal obesity is just emerging. Our group was one of the first to demonstrate that paternal obesity confers metabolic changes to the female offspring (Ng et al., 2010). Here we show that the male offspring are also impacted by their father's metabolic status. Sprague-Dawley rat fathers were fed either a control diet (CD-F0) or a high fat diet (HFD-F0) for 14 weeks before being mated with control females. The male offspring were weaned onto a control diet and killed either at 8 weeks or 6 months of age. Five weeks after weaning, the males from HFD-F0 showed a slow down in growth resulting in a significantly lower body weight from 9 weeks to 6 months of age. A decrease in plasma level of growth hormone and IGF1 was detected in 8 week old rats from HFD-F0. These rats presented smaller fat pads with a decrease in expression of Pparg and Igf1r in retro-peritoneal fat. In parallel, a decrease in expression of genes involved in muscle growth (Ghr, Igf1, mTOR and MyoD) was observed in tibialis anterioris muscle of males from HFD-F0. This resulted in smaller animals at 6 months of age that had smaller fat pads and muscles. The muscles of these rats showed ectopic lipid deposition with an increased expression of genes driving lipogenesis (Srebf1 and Fasn). The changes in growth and metabolism appeared to have no impact on glucose tolerance of 6 months old offspring. As observed in other models of programming (e.g. maternal low protein diet), investigating later stages of adulthood may uncover more direct metabolic consequences indicative of disease.
Physiological genomics, Jan 15, 2008
In this study we have identified the target genes of sterol regulatory element binding protein (S... more In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modified the mRNA level of 514 genes (310 upregulated and 204 downregulated). Gene ontology analysis indicated that in human muscle cells SREBP-1a and -1c are involved in the regulation of a large number of genes that are at the crossroads of different functional pathways, several of which are not directly connected with cholesterol and lipid metabolism. Six hundred fifty-two of all genes identified to be differentially regulated on SREBP overexpression had a sterol regulatory element (SRE) motif in their promoter sequences....
Obesity Research & Clinical Practice, 2013
Molecular and Cellular Biology, 2010
The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and... more The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.
Diabetes & Metabolism, 2008