FOXN3 controls liver glucose metabolism by regulating gluconeogenic substrate selection.

The FOXN3 gene locus is associated with fasting blood glucose levels in non-diabetic human population genetic studies. The blood glucose-modifying variation within this gene regulates the abundance of both FOXN3 protein and transcript in primary human hepatocytes, with the hyperglycemia risk allele causing increases in both FOXN3 protein and transcript. Using transgenic and knock-out zebrafish models, we showed previously that FOXN3 is a transcriptional repressor that regulates fasting blood glucose by altering liver gene expression of MYC, a  master transcriptional regulator of glucose utilization, and by modulating pancreatic α cell mass and function through an unknown mechanism.

FOXN3 hyperglycemic risk allele and insulin sensitivity in humans.

Objective: The rs8004664 variation within the FOXN3 gene is significantly and independently associated with fasting blood glucose in humans. We have previously shown that the hyperglycemia risk allele (A) increases FOXN3 expression in primary human hepatocytes; over-expression of human FOXN3 in zebrafish liver increases fasting blood glucose; and heterozygous deletion of the zebrafish ortholog decreases fasting blood glucose. Paralleling these model organism findings, we found that rs8004664 A|A homozygotes had blunted glucagon suppression during an oral glucose tolerance test.

Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor.

The fish-hunting marine cone snail uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this venom insulin, Con-Ins G1, has unique characteristics relevant to the design of new insulin therapeutics. Here, we show that fish-hunting cone snails provide a rich source of minimized ligands of the vertebrate insulin receptor.

The Monocarboxylate Transporter SLC16A6 Regulates Adult Length in Zebrafish and Is Associated With Height in Humans.

When fasted as larvae or fed ketogenic diets as adults, homozygous zebrafish mutants develop hepatic steatosis because their livers cannot export the major ketone body β-hydroxybutyrate, diverting liver-trapped ketogenic carbon atoms to triacylglycerol. Here, we find that mutants are longer than their wild-type siblings. This effect is largely not sexually dimorphic, nor is it affected by dietary fat content on a pure genetic background.

FOXN3 Regulates Hepatic Glucose Utilization.

A SNP (rs8004664) in the first intron of the FOXN3 gene is associated with human fasting blood glucose. We find that carriers of the risk allele have higher hepatic expression of the transcriptional repressor FOXN3. Rat Foxn3 protein and zebrafish foxn3 transcripts are downregulated during fasting, a process recapitulated in human HepG2 hepatoma cells.

Specialized insulin is used for chemical warfare by fish-hunting cone snails.

More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism.

Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice.

Lipid disorders pose therapeutic challenges. Previously we discovered that mutation of the hepatocyte β-hydroxybutyrate transporter Slc16a6a in zebrafish causes hepatic steatosis during fasting, marked by increased hepatic triacylglycerol, but not cholesterol. This selective diversion of trapped ketogenic carbon atoms is surprising because acetate and acetoacetate can exit mitochondria and can be incorporated into both fatty acids and cholesterol in normal hepatocytes.

A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting.

To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by adequate nutrition.

Influences of dietary biotin and avidin on growth, survival, deficiency syndrome and hepatic gene expression of juvenile Nile tilapia Oreochromis niloticus.

This study was undertaken to assess the interactive effects of dietary biotin and avidin on growth, feed conversion, survival and deficiency syndrome of tilapia and to determine the influence of dietary biotin deficiency on the expression of key genes related to biotin metabolism in tilapia. Six iso-nitrogenous and iso-energetic diets based on a common purified basal diet (vitamin-free casein as the protein source) were prepared for this study. The six dietary groups were 0 g avidin with 0 mg biotin (A0B0), 0 g avidin with 0.

Effects of dietary biotin and avidin on growth, survival, feed conversion, biotin status and gene expression of zebrafish Danio rerio.

A study was conducted to investigate the effects of dietary avidin on growth, survival, food conversion, biotin status and gene expression of zebrafish (Danio rerio Hamilton-Buchanan) juveniles (average wet mass 0.178 g) fed 7 purified diets for 12 weeks. Experimental diets were formulated to provide 0×, 1×, 15×, 30×, 60× and 120× excess avidin versus biotin kg(-1) diet, on a molar basis; a control diet contained neither supplemental biotin nor avidin.

Tandem duplication of the fabp1b gene and subsequent divergence of the tissue-specific distribution of fabp1b.1 and fabp1b.2 transcripts in zebrafish (Danio rerio).

We describe a fatty acid-binding protein 1 (fabp1b.2) gene and its tissue-specific expression in zebrafish embryos and adults. The 3.

Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio): evidence for subfunctionalization or neofunctionalization of duplicated genes.

Background: In the Duplication-Degeneration-Complementation (DDC) model, subfunctionalization and neofunctionalization have been proposed as important processes driving the retention of duplicated genes in the genome. These processes are thought to occur by gain or loss of regulatory elements in the promoters of duplicated genes. We tested the DDC model by determining the transcriptional induction of fatty acid-binding proteins (Fabps) genes by dietary fatty acids (FAs) in zebrafish.

The evolutionary relationship between the duplicated copies of the zebrafish fabp11 gene and the tetrapod FABP4, FABP5, FABP8 and FABP9 genes.

We describe the structure of a fatty acid-binding protein 11 (fabp11b) gene and its tissue-specific expression in zebrafish. The 3.4 kb zebrafish fabp11b is the paralog of the previously described zebrafish fabp11a, with a deduced amino acid sequence for Fabp11B exhibiting 65% identity with that of Fabp11A.