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. 2024 Apr;32(4):710-722.
doi: 10.1002/oby.23985. Epub 2024 Feb 4.

Antiobesity effects of intestinal gluconeogenesis are mediated by the brown adipose tissue sympathetic nervous system

Justine Vily-Petit  1   2   3 , Maud Soty-Roca  1   2   3 , Marine Silva  1   2   3 , Manon Micoud  1   2   3 , Félicie Evrard  1   2   3 , Clara Bron  1   2   3 , Margaux Raffin  1   2   3 , Daniel Beiroa  4   5 , Rubén Nogueiras  4   5 , Damien Roussel  2   3   6 , Amandine Gautier-Stein  1   2   3 , Fabienne Rajas  1   2   3 , Daniela Cota  7 , Gilles Mithieux  1   2   3
Affiliations

Antiobesity effects of intestinal gluconeogenesis are mediated by the brown adipose tissue sympathetic nervous system

Justine Vily-Petit et al. Obesity (Silver Spring). 2024 Apr.

Abstract

Objective: Intestinal gluconeogenesis (IGN), via the initiation of a gut-brain nervous circuit, accounts for the metabolic benefits linked to dietary proteins or fermentable fiber in rodents and has been positively correlated with the rapid amelioration of body weight after gastric bypass surgery in humans with obesity. In particular, the activation of IGN moderates the development of hepatic steatosis accompanying obesity. In this study, we investigated the specific effects of IGN on adipose tissue metabolism, independent of its induction by nutritional manipulation.

Methods: We used two transgenic mouse models of suppression or overexpression of G6pc1, the catalytic subunit of glucose-6 phosphatase, which is the key enzyme of endogenous glucose production specifically in the intestine.

Results: Under a hypercaloric diet, mice overexpressing IGN showed lower adiposity and higher thermogenic capacities than wild-type mice, featuring marked browning of white adipose tissue (WAT) and prevention of the whitening of brown adipose tissue (BAT). Sympathetic denervation restricted to BAT caused the loss of the antiobesity effects associated with IGN. Conversely, IGN-deficient mice exhibited an increase in adiposity under a standard diet, which was associated with decreased expression of markers of thermogenesis in both BAT and WAT.

Conclusions: IGN is sufficient to activate the sympathetic nervous system and prevent the expansion and the metabolic alterations of BAT and WAT metabolism under a high-calorie diet, thereby preventing the development of obesity. These data increase knowledge of the mechanisms of weight reduction in gastric bypass surgery and pave the way for new approaches to prevent or cure obesity.

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References

REFERENCES

    1. Segula D. Complications of obesity in adults: a short review of the literature. Malawi Med J. 2014;26(1):20‐24.
    1. Strissel KJ, Stancheva Z, Miyoshi H, et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes. 2007;56(12):2910‐2918. doi:10.2337/db07‐0767
    1. Kotzbeck P, Giordano A, Mondini E, et al. Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation. J Lipid Res. 2018;59(5):784‐794. doi:10.1194/jlr.M079665
    1. Lee M‐W, Lee M, Oh K‐J. Adipose tissue‐derived signatures for obesity and type 2 diabetes: adipokines, batokines and microRNAs. J Clin Med. 2019;8(6):854. doi:10.3390/jcm8060854
    1. Delaere F, Duchampt A, Mounien L, et al. The role of sodium‐coupled glucose co‐transporter 3 in the satiety effect of portal glucose sensing. Mol Metab. 2013;2(1):47‐53. doi:10.1016/j.molmet.2012.11.003

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