@article{fdi:010082806,
  title = {{I}ntestinal alteration of alpha-gustducin and sweet taste signaling pathway in metabolic diseases is partly rescued after weight loss and diabetes remission},
  author = {{L}e {G}leau, {L}. and {R}ouault, {C}. and {O}sinski, {C}. and {P}rifti, {E}di and {S}oula, {H}. {A}. and {D}ebedat, {J}. and {B}usieau, {P}. and {A}mouyal, {C}. and {C}lement, {K}. and {A}ndreelli, {F}. and {R}ibeiro, {A}. and {S}erradas, {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{C}arbohydrates and sweeteners are detected by the sweet taste receptor in enteroendocrine cells ({EEC}s). {T}his receptor is coupled to the gustducin {G}-protein, which alpha-subunit is encoded by {GNAT}3 gene. {I}n intestine, the activation of sweet taste receptor triggers a signaling pathway leading to {GLP}-1 secretion, an incretin hormone. {I}n metabolic diseases, {GLP}-1 concentration and incretin effect are reduced while partly restored after {R}oux-en-{Y} gastric bypass ({RYGB}). {W}e wondered if the decreased {GLP}-1 secretion in metabolic diseases is caused by an intestinal defect in sweet taste transduction pathway. {I}n our {RNA}-sequencing of {EEC}s, {GNAT}3 expression is decreased in patients with obesity and type 2 diabetes compared with normoglycemic obese patients. {T}his prompted us to explore sweet taste signaling pathway in mice with metabolic deteriorations. {D}uring obesity onset in mice, {G}nat3 expression was downregulated in {EEC}s. {A}fter metabolic improvement with enterogastro anastomosis surgery in mice (a surrogate of the {RYGB} in humans), the expression of {G}nat3 increased in the new alimentary tract and glucose-induced {GLP}-1 secretion was improved. {T}o evaluate if high-fat diet-induced dysbiotic intestinal microbiota could explain the changes in the expression of sweet taste alpha-subunit {G}-protein, we performed a fecal microbiota transfer in mice. {H}owever, we could not conclude if dysbiotic microbiota impacted or not intestinal {G}nat3 expression. {O}ur data highlight that metabolic disorders were associated with altered gene expression of sweet taste signaling in intestine. {T}his could contribute to impaired {GLP}-1 secretion that is partly rescued after metabolic improvement. {NEW} & {NOTEWORTHY} {O}ur data highlighted 1) the sweet taste transduction pathway in {EEC}s plays pivotal role for glucose homeostasis at least at gene expression level; 2) metabolic disorders lead to altered gene expression of sweet taste signaling pathway in intestine contributing to impaired {GLP}-1 secretion; and 3) after surgical intestinal modifications, increased expression of {GNAT}3, encoding a-gustducin contributed to metabolic improvement.},
  keywords = {alpha-gustducin ; intestinal endocrine cells ; microbiota ; obesity ; type 2 ; diabetes},
  booktitle = {},
  journal = {{A}merican {J}ournal of {P}hysiology.{E}ndocrinology and {M}etabolism},
  volume = {321},
  numero = {3},
  pages = {{E}417--{E}432},
  ISSN = {0193-1849},
  year = {2021},
  DOI = {10.1152/ajpendo.00071.2021},
  URL = {https://www.documentation.ird.fr/hor/fdi:010082806},
}