Dietary Alpha-Ketoglutarate Partially Abolishes Adverse Changes in the Small Intestine after Gastric Bypass Surgery in a Rat Model

Abstract

Alpha-ketoglutarate (AKG) is one of the key metabolites that play a crucial role in cellular energy metabolism. Bariatric surgery is a life-saving procedure, but it carries many gastrointestinal side effects. The present study investigated the beneficial effects of dietary AKG on the structure, integrity, and absorption surface of the small intestine after bariatric surgery. Male 7-week-old Sprague Dowley rats underwent gastric bypass surgery, after which they received AKG, 0.2 g/kg body weight/day, administered in drinking water for 6 weeks. Changes in small intestinal morphology, including histomorphometric parameters of enteric plexuses, immunolocalization of claudin 3, MarvelD3, occludin and zonula ocludens 1 in the intestinal mucosa, and selected hormones, were evaluated. Proliferation, mucosal and submucosal thickness, number of intestinal villi and Paneth cells, and depth of crypts were increased; however, crypt activity, the absorption surface, the expression of claudin 3, MarvelD3, occludin and zonula ocludens 1 in the intestinal epithelium were decreased after gastric bypass surgery. Alpha-ketoglutarate supplementation partially improved intestinal structural parameters and epithelial integrity in rats undergoing this surgical procedure. Dietary AKG can abolish adverse functional changes in the intestinal mucosa, enteric nervous system, hormonal response, and maintenance of the intestinal barrier that occurred after gastric bypass surgery.

Keywords: alpha-ketoglutaric acid; duodenum; gastric bypass; histomorphometry; jejunum.

Figure 1

Effect of bariatric surgery and administration of alpha-ketoglutarate (AKG) on body weight in rats. C—control, O—gastric bypass surgery, O + AKG—gastric bypass surgery and administration of alpha-ketoglutarate, AKG—administration of alpha-ketoglutarate. Alpha-ketoglutarate (0.2 g/kg/body mass/day) was administered in the drinking water.

Figure 2

Effects of bariatric surgery and alpha-ketoglutarate (AKG) administration on selected structural parameters of the duodenum and jejunum in rats. C—control, O—gastric bypass surgery, O + AKG—gastric bypass surgery and administration of alpha-ketoglutarate, AKG—administration of alpha-ketoglutarate. Alpha-ketoglutarate (0.2 g/kg/body mass/day) was administered in the drinking water. Different letters above the bars indicate significant differences at p < 0.05, and colors are used to indicate the corresponding intestinal segments.

Figure 3

Effects of bariatric surgery and alpha-ketoglutarate (AKG) administration on selected tight junction proteins of the intestinal barrier. (A) Representative images of the immunolocalization and distribution of claudin 3, MD3, occludin and Zo-1 in the rat duodenum. C—control group undergoing sham surgery; O—group undergoing gastric bypass surgery; O + AKG—group undergoing gastric bypass surgery and receiving alpha-ketoglutarate (AKG); AKG—group undergoing sham surgery and receiving alpha-ketoglutarate. AKG was administered at a dose of 0.2 g/kg/body weight/day in drinking water. All the scale bars represent 50 µ. (B) The bar graph shows the integrated intensity of immunoreactions, measured by comparing pixel brightness values adjusted to DAB staining color detection and inverted 8-bit grayscale, such that a higher pixel value reflects a higher immunoreaction intensity. Different letters above the bars indicate significant differences at p < 0.05, and colors are used to indicate the corresponding tight junction protein.

Figure 4

Effects of bariatric surgery and alpha-ketoglutarate (AKG) administration on selected tight junction proteins of the intestinal barrier. (A) Representative images of the immunolocalization and distribution of claudin 3, MD3, occludin and Zo-1 in the rat jejunum. C—control group undergoing sham surgery; O—group undergoing gastric bypass surgery; O + AKG—group undergoing gastric bypass surgery and receiving alpha-ketoglutarate (AKG); AKG—group undergoing sham surgery and receiving alpha-ketoglutarate. AKG was administered at a dose of 0.2 g/kg/body weight/day in drinking water. All the scale bars represent 50 µ. (B) The bar graph shows the integrated intensity of immunoreactions, measured by comparing pixel brightness values adjusted to DAB staining color detection and inverted 8-bit grayscale, such that a higher pixel value reflects a higher immunoreaction intensity. Different letters above the bars indicate significant differences at p < 0.05, and colors are used to indicate the corresponding tight junction protein.