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Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue.

Mardinoglu A, Heiker JT, Gärtner D, Björnson E, Schön MR, Flehmig G, Klöting N, Krohn K, Fasshauer M, Stumvoll M, Nielsen J, Blüher M - Sci Rep (2015)

Bottom Line: Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied.We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss.We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96, Gothenburg, Sweden.

ABSTRACT
Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss.

No MeSH data available.


Related in: MedlinePlus

Increased expression of the genes associated with the mitochondrial metabolic activity in SAT and VAT after extensive weight loss.Model for the expression of the genes involved in the transport of pyruvate from cytosol to mitochondria as well as the expression of the genes involved in the catabolism of branch chain amino acids in mitochondria is increased after extensive weight loss. Changes in gene expression before and after the extensive weight loss are highlighted in either red (higher expression) or blue (lower expression).
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f4: Increased expression of the genes associated with the mitochondrial metabolic activity in SAT and VAT after extensive weight loss.Model for the expression of the genes involved in the transport of pyruvate from cytosol to mitochondria as well as the expression of the genes involved in the catabolism of branch chain amino acids in mitochondria is increased after extensive weight loss. Changes in gene expression before and after the extensive weight loss are highlighted in either red (higher expression) or blue (lower expression).

Mentions: Previously, we have reported that the expression of the mitochondrial pyruvate carrier 1 (MPC1) and 2 (MPC2) that are essential for several major pathways of carbohydrate, fat, and amino acid metabolism55 are decreased in obesity50. In order to confirm the increased expression of the genes in the mitochondria after weight loss, we analyzed the expression of MPC1 and MPC2 using quantitative RT-PCR. We found that the expression of the MPC1 and MPC2 were significantly increased in SAT (Student’s t test, P-value  < 0.05) whereas the expression of MPC1 was significantly increased (Student’s t test, P-value < 0.05) in VAT after weight loss (Fig. 3). Increased expression of MPC1 and MPC2 in obese individuals after weight loss may indicate the increased mitochondrial activity in SAT and VAT of obese individuals having weight loss (Fig. 4). Moreover, we found that the expression of phosphoenolpyruvate carboxykinase 2 (PCK2), hydroxyacyl-CoA dehydrogenase (HADH) and aldehyde dehydrogenase 6 family, member A1 (ALDH6A1) are increased in the SAT mitochondria after weight loss.


Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue.

Mardinoglu A, Heiker JT, Gärtner D, Björnson E, Schön MR, Flehmig G, Klöting N, Krohn K, Fasshauer M, Stumvoll M, Nielsen J, Blüher M - Sci Rep (2015)

Increased expression of the genes associated with the mitochondrial metabolic activity in SAT and VAT after extensive weight loss.Model for the expression of the genes involved in the transport of pyruvate from cytosol to mitochondria as well as the expression of the genes involved in the catabolism of branch chain amino acids in mitochondria is increased after extensive weight loss. Changes in gene expression before and after the extensive weight loss are highlighted in either red (higher expression) or blue (lower expression).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4593186&req=5

f4: Increased expression of the genes associated with the mitochondrial metabolic activity in SAT and VAT after extensive weight loss.Model for the expression of the genes involved in the transport of pyruvate from cytosol to mitochondria as well as the expression of the genes involved in the catabolism of branch chain amino acids in mitochondria is increased after extensive weight loss. Changes in gene expression before and after the extensive weight loss are highlighted in either red (higher expression) or blue (lower expression).
Mentions: Previously, we have reported that the expression of the mitochondrial pyruvate carrier 1 (MPC1) and 2 (MPC2) that are essential for several major pathways of carbohydrate, fat, and amino acid metabolism55 are decreased in obesity50. In order to confirm the increased expression of the genes in the mitochondria after weight loss, we analyzed the expression of MPC1 and MPC2 using quantitative RT-PCR. We found that the expression of the MPC1 and MPC2 were significantly increased in SAT (Student’s t test, P-value  < 0.05) whereas the expression of MPC1 was significantly increased (Student’s t test, P-value < 0.05) in VAT after weight loss (Fig. 3). Increased expression of MPC1 and MPC2 in obese individuals after weight loss may indicate the increased mitochondrial activity in SAT and VAT of obese individuals having weight loss (Fig. 4). Moreover, we found that the expression of phosphoenolpyruvate carboxykinase 2 (PCK2), hydroxyacyl-CoA dehydrogenase (HADH) and aldehyde dehydrogenase 6 family, member A1 (ALDH6A1) are increased in the SAT mitochondria after weight loss.

Bottom Line: Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied.We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss.We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96, Gothenburg, Sweden.

ABSTRACT
Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss.

No MeSH data available.


Related in: MedlinePlus