modif cell nitestinale ap chir baria 2017 pharma.pdf

Aperçu du fichier PDF modif-cell-nitestinale-ap-chir-baria-2017-pharma.pdf

Page 1 2 3 4 5 6

Aperçu texte

Available online at

Intestinal adaptations following bariatric surgery:
towards the identification of new pharmacological
targets for obesity-related metabolic diseases
Lara Ribeiro-Parenti1, Jean-Baptiste Cavin1,2 and
Maude Le Gall1
Although the gastrointestinal tract is the primary target of
bariatric surgery, its contributions to the metabolic changes
observed after surgery are still underestimated. Changes in the
number of incretin-producing cells could result in the modified
hormonal response seen after surgery. Additionally, the rate of
absorption and consumption of glucose could contribute to the
ameliorated glycaemia. Moreover, decreased intestinal
permeability could prevent endotoxemia.Recently, numerous
studies have focused on intestinal adaptation following
bariatric surgeries. These studies bring new insight into the
different roles the GI tract plays in the metabolic outcomes of
bariatric surgery and open new avenues for therapeutic
Inserm UMR 1149, UFR de Me´decine Paris Diderot, Universite´ Paris
Diderot, Sorbonne Paris Cite´, DHU Unity APHP, F-75890 Paris, France
Department of Physiology and Pharmacology, Hotchkiss Brain
Institute, University of Calgary, Alberta, T2N4N1 Calgary, Canada
Corresponding author: Le Gall, Maude (

Current Opinion in Pharmacology 2017, 37:29–34
This review comes from a themed issue on Endocrine and metabolic
Edited by Gavin Bewick
For a complete overview see the Issue and the Editorial
Available online 17th August 2017
1471-4892/ã 2017 Elsevier Ltd. All rights reserved.

emptying, carbohydrate digestion, and glucose absorption
during and between meals. Meanwhile, alteration of the
GI barrier function is increasingly recognized as a key
player in metabolic disease development through endotoxemia. The point of this review is to illustrate how the
adaptation of the GI tract may play important roles in the
metabolic changes induced by bariatric surgeries and how
this adaptation could be targeted by new pharmacological
drugs delivered per os to bypass the surgery.
Bariatric surgery

The most commonly performed bariatric surgeries worldwide are sleeve gastrectomy and Roux-en-Y gastric
bypass (RYGB) (Figure 1). Sleeve gastrectomy consists
of the resection of three quarters of the stomach, removing the fundus and part of the gastric body. Although it
does not physically rearrange the intestinal tract, it modifies the intestinal luminal content by accelerating gastric
emptying and decreasing stomach secretory activity. The
bypass procedure, on the other hand, profoundly modifies
the intestinal tract. In addition to the creation of a small
gastric pouch, the chyme is directly discharged from the
stomach into a more distal part of the jejunum; thereby,
bypassing the duodenum and a large part of the jejunum.
RYGB is thus considered to be malabsorptive although
the intestine rapidly adapts and compensates for this
malabsorption [1]. Historically, bariatric surgeries were
designed to promote weight loss however their benefits
on obesity comorbidities are far beyond and even independent of weight loss [2].
Enteroendocrine cells after bariatric surgery

The main gastro-intestinal (GI) functions (i.e. absorption,
secretion and its barrier) can be modulated according to
environmental factors, food composition, and metabolic
state, they have even been shown to be altered by
bariatric surgeries. For instance, the GI tract is the largest
endocrine organ of the body and produces a set of
hormones, including incretins that regulate the release
of insulin. Alterations in incretin secretions after bariatric
surgeries are well characterized but their origins are still a
matter of debate. In addition, the GI tract plays a direct
role in glucose homeostasis by modulating gastric

Modulation of gut hormone secretion is a pivotal aspect
underlying the beneficial metabolic effects of bariatric
surgeries. Hormonal changes are numerous after surgery,
and depend on the type of GI reconstruction [3,4].
Exacerbated GLP-1 secretion is notably suspected to
contribute to most metabolic improvements observed
after bariatric surgery, regardless of weight loss [5].
The origin of the modified hormonal secretions is still
highly debated. The two main overlapping hypotheses
propose that altered nutrient flow, either by duodenal
exclusion or by accelerated hindgut delivery of nutrients
(also called the ‘foregut’ and ‘hindgut’ hypotheses), are
responsible for the altered hormonal response. They
could drive the success of not only RYGB [6], but also
of VSG as gastric emptying rates are very rapid after this
Current Opinion in Pharmacology 2017, 37:29–34