scholarly journals Impact of Fibroblast Growth Factors 19 and 21 in Bariatric Metabolism

2017 ◽  
Vol 35 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Ashley Patton ◽  
Farooq H. Khan ◽  
Rohit Kohli
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Bile Acid ◽  
Health Condition ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Fibroblast Growth ◽  
Long Term Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Distal Small Intestine

Background: Bariatric surgery is a popular and effective therapeutic intervention for obesity, which is an abnormal health condition that is prevalent worldwide. Metabolic improvements that precede weight loss after bariatric surgery may be mediated, in part, through the fibroblast growth factor (FGF) 15/19 and FGF21 signaling pathways. Both FGF15/19 and FGF21 are hormone-like members of the FGF family and exert their metabolic effects in an endocrine manner. Enhanced bile acid recycling after bariatric surgery leads to increased circulating levels of FGF15/19 in the distal small intestine. Synthesis of FGF21 is upregulated predominately in the fasting state through peroxisome proliferator-activated receptor pathways and to a lesser extent by FGF15/19. Key Messages: The biological functions of FGF15/19 and FGF21 are diverse and complicated. The tissue targeted effects of FGF15/19 and FGF21 of importance after bariatric surgery include the regulation of hepatic bile acid biosynthesis and ketogenesis as well as thermogenesis in adipose tissue, respectively. Furthermore, FGF15/19 and FGF21 function to regulate carbohydrate and lipid metabolism. Conclusion: The long-term effects of bariatric surgery on weight loss are undisputable. However, the mechanism for improvements in glucose and lipid homeostasis observed shortly after bariatric surgery is less understood. This review article attempts to describe the known metabolic effects of FGF15/19 and FGF21 that may potentiate these improvements after bariatric surgery.

scholarly journals Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity

2020 ◽  
Author(s):  
Rafael Ferraz-Bannitz ◽  
Caroline Rossi Welendorf ◽  
Priscila Oliveira Coelho ◽  
Wilson Salgado ◽  
Carla Barbosa Nonino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Strong Positive Correlation ◽  
Peroxisome Proliferator Activated Receptor

Abstract Background Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB) is the most effective and durable treatment option for population with severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery. Methods We aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB. Results Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3M and 6M Post-RYGB showed that interleukins (Interleukin 6, Tumor necrosis factor-α (TNF-α), and Monocyte chemoattractant protein-1(MCP1)) and endoplasmic reticulum stress (ERS) genes (Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)) decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis (Adiponectin and AMP-activated protein kinase (AMPK)), cellular response to oxidative stress (Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)), mitochondrial biogenesis (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)) and amino acids metabolism (General control nonderepressible 2 (GCN2)) increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05) We also observed a strong positive correlation between PGC1α, SIRT1 and AMPK with BMI at 3M (P ≤ 0.01 for all) and ADIPOQ and SIRT1 with BMI at 6M (P ≤ 0.01 for all). Conclusions Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB.

scholarly journals Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Rafael Ferraz-Bannitz ◽  
Caroline Rossi Welendorf ◽  
Priscila Oliveira Coelho ◽  
Wilson Salgado ◽  
Carla Barbosa Nonino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Strongly Correlated ◽  
Peroxisome Proliferator Activated Receptor

Abstract Background Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery. Methods We aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB. Results Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3 M and 6 M Post-RYGB showed that interleukins [Interleukin 6, Tumor necrosis factor-α (TNF-α), and Monocyte chemoattractant protein-1(MCP1)] and endoplasmic reticulum stress (ERS) genes [Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)] decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3 M (P ≤ 0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6 M (P ≤ 0.01 for all). Conclusions Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB. Trial registration CAAE: 73,585,317.0.0000.5440

scholarly journals Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity

2020 ◽  
Author(s):  
Rafael Ferraz-Bannitz ◽  
Caroline Rossi Welendorf ◽  
Priscila Oliveira Coelho ◽  
Wilson Salgado ◽  
Carla Barbosa Nonino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Strongly Correlated ◽  
Peroxisome Proliferator Activated Receptor

Abstract Background: Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.Methods: We aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB.Results: Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3M and 6M Post-RYGB showed that interleukins (Interleukin 6, Tumor necrosis factor-α (TNF-α), and Monocyte chemoattractant protein-1(MCP1)) and endoplasmic reticulum stress (ERS) genes (Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)) decreased during the follow-up (P≤0.01 for all). Otherwise, genes involved in energy homeostasis (Adiponectin and AMP-activated protein kinase (AMPK)), cellular response to oxidative stress (Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)), mitochondrial biogenesis (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)) and amino acids metabolism (General control nonderepressible 2 (GCN2)) increased from baseline to all other time points evaluated (P≤0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P<0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3M (P≤0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6M (P≤0.01 for all).Conclusions: Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB.Trial registration: CAAE: 73585317.0.0000.5440

scholarly journals Bile Acid Signaling: Mechanism for Bariatric Surgery, Cure for NASH?

2015 ◽  
Vol 33 (3) ◽  
pp. 440-446 ◽  
Author(s):  
Rohit Kohli ◽  
Andriy Myronovych ◽  
Brandon K. Tan ◽  
Rosa-Maria Salazar-Gonzalez ◽  
Lili Miles ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Adjustable Gastric Band ◽  
Metabolic Effects ◽  
Signaling Mechanism ◽  
Serum Bile Acids ◽  
Long Run

Bariatric surgery is the most effective and durable treatment option for obesity today. More importantly, beyond weight loss, bariatric procedures have many advantageous metabolic effects including reversal of obesity-related liver disease - nonalcoholic steatohepatitis (NASH). NASH is an important comorbidity of obesity given that it is a precursor to the development of liver cirrhosis that may necessitate liver transplantation in the long run. Simultaneously, we and others have observed increased serum bile acids in humans and animals that undergo bariatric surgery. Specifically, our preclinical studies have included experimental procedures such as ‘ileal transposition' or bile diversion and established procedures such as Roux-en-Y gastric bypass and the adjustable gastric band. Importantly, these effects are not simply the result of weight loss since our data show that the resolution of NASH and increase in serum bile acids are not seen in rodents that lose an equivalent amount of weight via food restriction. In particular, we have studied the role of altered bile acid signaling, in the potent impact of a bariatric procedure termed ‘vertical sleeve gastrectomy' (VSG). In this review we focus on the mechanisms of NASH resolution and weight loss after VSG surgery. We highlight the fact that bariatric surgeries can be used as ‘laboratories' to dissect the mechanisms by which these procedures work to improve obesity and fatty liver disease. We describe key bile acid signaling elements that may provide potential therapeutic targets for ‘bariatric-mimetic technologies' that could produce benefits similar to bariatric surgery - but without the surgery!

scholarly journals Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity

2020 ◽  
Author(s):  
Rafael Ferraz-Bannitz ◽  
Caroline Rossi Welendorf ◽  
Priscila Oliveira Coelho ◽  
Wilson Salgado ◽  
Carla Barbosa Nonino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Strongly Correlated ◽  
Peroxisome Proliferator Activated Receptor

Abstract Background: Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.Methods: We aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB. Results: Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3M and 6M Post-RYGB showed that interleukins (Interleukin 6, Tumor necrosis factor-α (TNF-α), and Monocyte chemoattractant protein-1(MCP1)) and endoplasmic reticulum stress (ERS) genes (Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)) decreased during the follow-up (P≤0.01 for all). Otherwise, genes involved in energy homeostasis (Adiponectin and AMP-activated protein kinase (AMPK)), cellular response to oxidative stress (Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)), mitochondrial biogenesis (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)) and amino acids metabolism (General control nonderepressible 2 (GCN2)) increased from baseline to all other time points evaluated (P≤0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P<0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3M (P≤0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6M (P≤0.01 for all). Conclusions: Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB.

scholarly journals Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Univariate Analysis ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects ◽  
Daily Ingestion ◽  
Before And After ◽  
Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

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