Time-Dependent Molecular Responses Differ between Gastric Bypass and Dieting but Are Conserved Across Species

Ben‐Zvi, Danny; Meoli, Luca; Abidi, Wasif M.; Nestoridi, Eirini; Panciotti, Courtney; Castillo, Erick; Pizarro, Palmenia; Shirley, Eleanor; Gourash, William; Thompson, Christopher C.; Muñóz, Rodrigo; Clish, Clary B.; Anafi, Ron C.; Courcoulas, Anita P.; Stylopoulos, Nicholas

doi:10.1016/j.cmet.2018.06.004

Cited by 50 publications

(49 citation statements)

References 60 publications

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“…In our pilot study, the length of BP limb and AL limb were first set to be 6 cm each [13] which lead to death within 5 weeks due to malnutrition. Thus in this study we shorten the length of both limb to be 4cm each, which resulted in 36±3.7% average body weight loss without death from malnutrition, as comparable to other report [14]. Although creating a small gastric pouch with volume of 30ml (using a balloon gastric tube for measurement) is a standard step of RYGB in human [15], it is debatable to use such gastric pouch on mouse model [10,13,16].…”

Section: Discussionsupporting

confidence: 70%

Increased Energy Expenditure and Energy Loss through Feces Contribute to the Long-term Outcome of Roux-en-Y Gastric Bypass on Diet Induced Obese Mouse Model

Chen¹,

Xiao²,

Zhou³

et al. 2020

Preprint

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Background Roux-en-Y gastric bypass (RYGB) has been proved to be more effective than other bariatric procedures in long-term on body weight loss and remission of diabetes. However, the mechanism remains poorly understood. Long-term change of energy metabolism after RYGB has rarely been reported. Objectives To investigate the long-term outcome of RYGB on mouse model and its mechanism from the perspective of energy metabolism. Methods High-fat diet induced obesity (DIO) mice were assigned to two groups receiving RYGB(n=8) and sham operation(n=7), followed by high-fat diet feeding until 12 weeks after surgery. Body weight and food intake were recorded weekly, measurement of body composition and energy metabolism by metabolic chamber were conducted on week 4, 8 and 12 after surgery. Fecal energy measurement, Intraperitoneal Glucose Tolerance Test (IPGTT) and Insulin Tolerance Test (ITT) were conducted on week 12 after surgery.Results Food intake was reduced in RYGB group within the first 3 weeks after surgery and increased to be the same withSham group from postoperative week 4. At 12 weeks after surgery, body weight reduced by 36±3.2% in RYGB group comparing to 16±2% body weight gain in Sham group, while fat mass was significantly reduced in RYGB group than in Sham group (9.2±1.5% versus 30.1±0.7%). Energy expenditure was significantly higher on postoperative week 8 in RYGB group than in Sham group. In comparison with Sham group, respiratory exchange ratio (RER) was unchanged, decreased and increased in RYGB group at postoperative week 4, 8 and 12, respectively. Fecal energy measurementshowed that feces from mice in RYGB group contained higher energy level than Sham group. Glucose metabolism was significantly improved in RYGB group in contrast to Sham group, demonstrated by the result of Intraperitoneal Glucose Tolerance Test (IPGTT) (AUC: 1502± 104 versus 2277±198, respectively) and the Insulin Tolerance Test (ITT) (AUC: 524 ±50 versus 838±63, respectively). Conclusions Increased energy expenditure and energy loss through feces contribute to the long-term body weight control after RYGB. Enhanced glucose utilization might play a role in the long-term improvement of glucose metabolism.

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Section: Discussionsupporting

confidence: 70%

Increased Energy Expenditure and Energy Loss through Feces Contribute to the Long-term Outcome of Roux-en-Y Gastric Bypass on Diet Induced Obese Mouse Model

Chen¹,

Xiao²,

Zhou³

et al. 2020

Preprint

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“…To date, most murine studies of SG have utilized a diet-induced model of obesity (DIO) or a genetically obese model, combined with sham pair-feeding, in an attempt to recapitulate and study SG physiology. [9,11,14,15,[39][40][41] While mice in these studies become obese and have hyperglycemia similar to the target patient population, investigations are limited by differences in food intake via pair-feeding and/or differences in body weight between the surgical intervention and sham groups. Furthermore, in most experiments, pair feeding induces weight loss.…”

Section: Discussionmentioning

confidence: 99%

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

Harris

Mina

Čabarkapa

et al. 2019

Preprint

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Objective: Sleeve gastrectomy (SG) induces weight-loss independent improvements in glucose homeostasis by unknown mechanisms. We sought to identify the metabolic adaptations responsible for these improvements.Methods: Non-obese C57Bl6/J mice on standard chow underwent SG or sham surgery. Functional testing and indirect calorimetry were used to capture metabolic phenotypes. Tissuespecific glucose uptake was assessed by 18-FDG PET/CT and RNA sequencing was used for gene expression analysis.Results: In this model, SG induced durable improvements in glucose tolerance despite not causing lasting changes in weight, fat/lean mass, or food intake. Indirect calorimetry revealed post-SG animals had respiratory exchange ratios (RER) nearing 1.0 on average and had daily RER excursions above 1.0, indicating preferential glucose utilization and increased energy demand, respectively. Sham operated mice demonstrate normal RER feeding/fasting excursions. PET/CT showed increased avidity within white adipose depots. Finally, SG led to an upregulation in the transcriptional pathways involved in energy metabolism, adipocyte maturation, and adaptive and innate immune cell chemotaxis and differentiation within the visceral adipose tissue.Conclusions: SG induces a rapid, weight-loss independent shift towards glucose utilization and transcriptional remodeling of metabolic and immune pathways in visceral adipose tissue.

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“…Further, in a comprehensive tissue-wide translational study, Ben-Zvi et al (91) demonstrated using RNAsequencing that Ucp1 and Cidea mRNA expressions are higher in the inguinal WAT of RYGB-operated high-fat diet-induced obese male C57BL/6 mice compared to BWM sham-operated mice, as was UCP1 protein expression determined by representative immunohistochemistry. Importantly, this was complemented with indirect calorimetry measurements which confirmed higher energy expenditure in RYGB-operated mice compared to BWM sham-operated mice (91). While the underlying causal mechanisms for enhanced BeAT thermogenesis after RYGB compared to chronic caloric restriction-induced weight loss were not established in this particular study, mRNA expression of the anti-inflammatory cytokine interleukin-33 (Il33) was markedly increased in the inguinal WAT of RYGB-operated mice (91).…”

Section: Rygb and Bat/beat Thermogenesismentioning

confidence: 74%

Do Bariatric Surgeries Enhance Brown/Beige Adipose Tissue Thermogenesis?

Hankir

Seyfried

2020

Front. Endocrinol.

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Bariatric surgeries induce marked and durable weight loss in individuals with morbid obesity through powerful effects on both food intake and energy expenditure. While alterations in gut-brain communication are increasingly implicated in the improved eating behavior following bariatric surgeries, less is known about the mechanistic basis for energy expenditure changes. Brown adipose tissue (BAT) and beige adipose tissue (BeAT) have emerged as major regulators of whole-body energy metabolism in humans as well as in rodents due to their ability to convert the chemical energy in circulating glucose and fatty acids into heat. In this Review, we critically discuss the steadily growing evidence from preclinical and clinical studies suggesting that Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), the two most commonly performed bariatric surgeries, enhance BAT/BeAT thermogenesis. We address the documented mechanisms, highlight study limitations and finish by outlining unanswered questions in the subject. Further understanding how and to what extent bariatric surgeries enhance BAT/BeAT thermogenesis may not only aid in the development of improved obesity pharmacotherapies that safely and optimally target both sides of the energy balance equation, but also in the development of novel hyperglycemia and/or hyperlipidemia pharmacotherapies.

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Time-Dependent Molecular Responses Differ between Gastric Bypass and Dieting but Are Conserved Across Species

Cited by 50 publications

References 60 publications

Increased Energy Expenditure and Energy Loss through Feces Contribute to the Long-term Outcome of Roux-en-Y Gastric Bypass on Diet Induced Obese Mouse Model

Increased Energy Expenditure and Energy Loss through Feces Contribute to the Long-term Outcome of Roux-en-Y Gastric Bypass on Diet Induced Obese Mouse Model

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

Do Bariatric Surgeries Enhance Brown/Beige Adipose Tissue Thermogenesis?

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