Low Protein Intake Is Associated with Reduced Hepatic Gluconeogenic Enzyme Expression in Rainbow Trout (Oncorhynchus mykiss)

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SUMMARYThis study was designed to assess the effects of dietary fat levels on glucose homeostasis in rainbow trout under prolonged hyperglycaemia induced by high carbohydrate intake. Trout were fed identical amounts of one of two iso-energetic diets containing either a low (LFD, 3%) or a high fat level (HFD, 20%) and similar amounts of digestible carbohydrates (26-30%) for 14days. While a single high fat meal reduced glycaemia compared with a low fat meal, the consumption of a high fat diet for 14days resulted in prolonged hypergylcaemia and reduced plasma glucose clearance in response to an exogenous glucose or insulin challenge. The hyperglycaemic phenotype in trout was characterised by a reduction of the activities of lipogenic and glucose phosphorylating enzymes with a concomitant stimulation of enzymes involved in glucose production in the liver and reduced glycogen levels in the white muscle. Impaired glucose tolerance (IGT) was further associated with a significant reduction of insulin receptor substrate 1 (IRS1) protein content in muscle, and with a poor response of HFD fed fish to an exogenous insulin load, suggestive of impaired insulin signalling in trout fed with a HFD. To our knowledge, this is the first study showing that a teleost can also develop a high fat-induced IGT, characterised by persistent hyperglycaemia and reduced insulin sensitivity, established symptoms of IGT and the prediabetic insulin-resistant state in mammals. Our results also provide evidence that persistent hyperglycaemia after a high carbohydrate meal stems from a metabolic interaction between dietary macronutrients rather than from high carbohydrate intake alone.

Section: Metabolic Events Linked To the Hfd-induced Hyperglycaemiamentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

High levels of dietary fat impair glucose homeostasis in rainbow trout

Figueiredo-Silva

Panserat

Kaushik

et al. 2012

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“…In fish, the relative importance of the two pathways has not been established, and both may contribute to R a glucose under our conditions. For carnivorous species like rainbow trout, however, gluconeogenesis from amino acid precursors is known to play an important role (Kirchner et al, 2003;Polakof et al, 2012). What are the mechanisms responsible for suppressing glycogenolysis and/or gluconeogenesis in trout responding to exogenous glucose?…”

Section: Suppression Of Hepatic Glucose Productionmentioning

confidence: 99%

Pushing the limits of glucose kinetics: how rainbow trout cope with a carbohydrate overload

Choi

Weber

2015

Rainbow trout are generally considered to be poor glucoregulators. To evaluate this, exogenous glucose was administered to chronically hyperglycemic fish at twice the endogenous rate of hepatic production, and their ability to modulate glucose fluxes was tested. Our goals were to determine: (1) whether hyperglycemic fish maintain higher glucose fluxes than normal; (2) whether they can lower hepatic production (R a glucose) or stimulate disposal (R d glucose) to cope with a carbohydrate overload; and (3) an estimate of the relative importance of glucose as an oxidative fuel. Results show that hyperglycemic trout sustain elevated baseline R a and R d glucose of 10.6±0.1 µmol kg −1 min −1 (or 30% above normal). If 50% of R d glucose was oxidized as in mammals, glucose could account for 36 to 100% of metabolic rate when exogenous glucose is supplied. In response to exogenous glucose, rainbow trout can completely suppress hepatic glucose production and increase disposal 2.6-fold, even with chronically elevated baseline fluxes. Such large changes in fluxes limit the increase in blood glucose to 2.5-fold and are probably mediated by the effects of insulin on glucose transporters 2 and 4 and on key enzymes of carbohydrate metabolism. Without this strong and rapid modulation of glucose kinetics, glycemia would rise four times faster to reach dangerous levels, exceeding 100 mmol l −1. Such responses are typical of mammals, but rather unexpected for an ectotherm. The impressive plasticity of glucose kinetics demonstrated here suggests that trout have a much better glucoregulatory capacity than is usually portrayed in the literature.

“…This consistently high dietary amino acid intake can thus have undesirable effects on insulin sensitivity, particularly on insulin-regulated gene expression. This could explain the absence of post-prandial down regulation of the expression of insulin target genes such as G6Pase and PEPCK and the restoration of their inhibition by reducing dietary protein levels (Kirchner et al, 2003). Further experiments are needed to examine this hypothesis and to analyze the effects of excessive amino acids on the regulation of the hepatic target gene by insulin.…”

Section: Perspective and Significancementioning

confidence: 99%

Insulin regulates the expression of several metabolism-related genes in the liver and primary hepatocytes of rainbow trout (Oncorhynchus mykiss)

Plagnes-Juan

Lansard

Seiliez

et al. 2008

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104

SUMMARYRainbow trout have a limited ability to use dietary carbohydrates efficiently and are considered to be glucose intolerant. Administration of carbohydrates results in persistent hyperglycemia and impairs post-prandial down regulation of gluconeogenesis despite normal insulin secretion. Since gluconeogenic genes are mainly under insulin control, we put forward the hypothesis that the transcriptional function of insulin as a whole may be impaired in the trout liver. In order to test this hypothesis, we performed intraperitoneal administration of bovine insulin to fasted rainbow trout and also subjected rainbow trout primary hepatocytes to insulin and/or glucose stimulation. We demonstrate that insulin was able to activate Akt, a key element in the insulin signaling pathway, and to regulate hepatic metabolism-related target genes both in vivo and in vitro. In the same way as in mammals, insulin decreased mRNA expression of gluconeogenic genes, including glucose 6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase (PEPCK). Insulin also limited the expression of carnitine palmitoyltransferase 1 (CPT1), a limiting enzyme of fatty acid β-oxidation. In vitro studies revealed that, as in mammals, glucose is an important regulator of some insulin target genes such as the glycolytic enzyme pyruvate kinase (PK) and the lipogenic enzyme fatty acid synthase (FAS). Interestingly, glucose also stimulates expression of glucokinase (GK), which has no equivalent in mammals. This study demonstrates that insulin possesses the intrinsic ability to regulate hepatic gene expression in rainbow trout, suggesting that other hormonal or metabolic factors may counteract some of the post-prandial actions of insulin.