Dietary Tryptophan Supplementation Alters Fat and Glucose Metabolism in a Low-Birthweight Piglet Model

Abstract

Low birthweight (LBW) is associated with metabolic complications, such as glucose and lipid metabolism disturbances in early life. The objective of this study was to assess: (1) the effect of dietary tryptophan (Trp) on glucose and fat metabolism in an LBW piglet model, and (2) the role peripheral 5-hydroxytryptamine type 3 (5HT3) receptors in regulating the feeding behavior in LBW piglets fed with Trp-supplemented diets. Seven-day-old piglets were assigned to 4 treatments: normal birthweight-0%Trp (NBW-T0), LBW-0%Trp (LBW-T0), LBW-0.4%Trp (LBW-T0.4), and LBW-0.8%Trp (LBW-T0.8) for 3 weeks. Compared to LBW-T0, the blood glucose was decreased in LBW-T0.8 at 60 min following the meal test, and the triglycerides were lower in LBW-T0.4 and LBW-T0.8. Relative to LBW-T0, LBW-T0.8 had a lower transcript and protein abundance of hepatic glucose transporter-2, a higher mRNA abundance of glucokinase, and a lower transcript of phosphoenolpyruvate carboxykinase. LBW-T0.4 tended to have a lower protein abundance of sodium-glucose co-transporter 1 in the jejunum. In comparison with LBW-T0, LBW-T0.4 and LBW-T0.8 had a lower transcript of hepatic acetyl-CoA carboxylase, and LBW-T0.4 had a higher transcript of 3-hydroxyacyl-CoA dehydrogenase. Blocking 5-HT3 receptors with ondansetron reduced the feed intake in all groups, with a transient effect on LBW-T0, but more persistent effect on LBW-T0.8 and NBW-T0. In conclusion, Trp supplementation reduced the hepatic lipogenesis and gluconeogenesis, but increased the glycolysis in LBW piglets. Peripheral serotonin is likely involved in the regulation of feeding behavior, particularly in LBW piglets fed diets supplemented with a higher dose of Trp.

A Mixture of Valine and Isoleucine Restores the Growth of Protein-Restricted Pigs Likely through Improved Gut Development, Hepatic IGF-1 Pathway, and Plasma Metabolomic Profile

“…The experimental diets were analyzed for dry matter, CP, crude fat, crude fiber, calcium, phosphorus, and N by Servi-Tech laboratory (Dodge City, KS, USA) as we previously described [ 4 , 8 , 54 ]. Dietary AA concentration was quantified at Agricultural Experiment Station Chemical Laboratories (University of Missouri-Columbia, MO, USA) following previously published procedures [ 55 ]. The result of the above analysis is presented in Table 5 .…”

“…As we previously described [ 55 ], thermal images were analyzed using FLIR Research Studio software (FLIR Systems, Boston, MA, USA). For obtaining the dorsal surface mean body temperature, a rectangular shape was drawn in the region of interest (i.e., from shoulder to the rump; Supplementary Figure S3 ).…”

“…Gut segments were coated in paraffin and cut into 5 μm sections. Following staining, the sections with hematoxylin and eosin, using a BZ-X800E Keyence all-in-one fluorescence microscope (BZ-X710, IL, USA) at least, ten well-oriented villi and crypt in each section were considered to measure villus height and width, crypt depth and width, and muscle thickness [ 55 ]. Images were captured by Keyence BZ-X Viewer (Keyence Co. USA, Itasca, IL, USA) and analyzed using ImageJ software ( ; accessed on 13 June 2021).…”

Gut microbiota-derived tryptamine impairs insulin sensitivity

“…We then studied whether the precursor (Trp) or metabolite (IAA) of tryptamine can affect glucose tolerance or insulin sensitivity. Trp has been shown to suppress glucose level and preserves insulin secretion in vivo (Goodarzi et al, 2021; Inubushi et al, 2012), and no significant difference in blood glucose level between the control group and IAA-treated group was found in the OGTT experiment (Supplement Figure. S3D).…”

“…We then studied whether the precursor (Trp) or metabolite (IAA) of tryptamine can affect glucose tolerance or insulin sensitivity. Trp has been shown to suppress glucose level and preserves insulin secretion in vivo (Goodarzi et al, 2021;Inubushi et al, 2012), and no significant difference in blood glucose level between the control group and IAA-treated group was found in the OGTT experiment (Supplement Figure .S3D). Moreover, Trp and IAA treatment did not affect the AKT phosphorylation in insulin-stimulated 3T3-L1 cells (Supplement Figure .S3E), suggesting tryptamine but not its precursor or metabolite can impair glucose tolerance and insulin sensitivity.…”