Is high fat diet induced FGF21 expression in epididymal adipose tissue affected by the addition of the rare sugar sweetener allulose?

Background

Fibroblast Growth Factor 21 (FGF21) is a pleiotropic peptide hormone which is expressed across a variety of different metabolically active tissues in mammals. FGF21 is part of the FGF19 subfamily of the FGF superfamily, and has a broad range of effects, depending on concentration, metabolic factors, and region in which it is expressed. FGF21 has been described as the “Starvation Hormone” as it is robustly expressed in hypo energetic diets and promotes several notable health benefits, such as glycaemic control, longevity and upregulating glucose neogenesis. FGF21 is also shown to be associated with negative health conditions and has been suggested for use as a biomarker, particularly for Liver conditions such as Non-Alcoholic Fatty Liver Disease (NAFLD) and mitochondrial disorders. Similarly, unhealthier diets, such as those higher in saturated fats, carbohydrates and free sugars are all shown to increase FGF21 levels. The objective of this study will be to analyse the RNA expression of FGF21, alongside the overall effect of Allulose supplementation to a high fat diet.

Methods:

C57/BL6 mice were exposed to an array of experimental diets in a previous study, Lean Diet (LD), High Fat Diet (HFD), Allulose (HFDa) and Fructose (HFDf). Serum expression levels of FGF21 amongst other metrics were measured during the course of this initial experiment. In this study, tissue samples from these test subjects were analysed. Liver sections were subjected to histological stains, and Epididymal Adipose Tissues from each group were analysed for FGF21 RNA expression. Quantitative Polymerase Chain Reaction (qPCR) was utilised to analyse this RNA expression, in conjunction with the housekeeping gene Peptidylprolyl Isomerase A (PPIA).

Results:

The addition of Allulose to the drinking water in HFD’s induces a -1.73-fold change relative to HFDw FGF21 RNA expression levels, whereas the addition of Fructose induces a -0.23-fold change relative to HFDw FGF21 RNA expression levels. HFDw, relative to LDw, experiences a -0.4-fold expression change. Furthermore, weight gain was significantly reduced with the addition of Allulose to HFD, whereas the serum expression of FGF21 rose to near LDw levels. Lipid accumulation is also ameliorated with the addition of Allulose, decreasing TG content to near- LDw levels. OGTT metrics are also decreased, indicative that glycaemic control is improved overall, promoting insulin sensitivity.

Conclusion:

The addition of Allulose to High Fat Diets ameliorates the worse conditions associated with this diet: obesity, worsened glycaemic control, insulin insensitivity. Allulose induced the serum expression of FGF21, which returned to near-normal levels when compared to HFD+ water diet. Moreover, Allulose decreased Epididymal Adipose Tissue FGF21 RNA expression, a 170% drop when compared to HFD. Despite localised downregulation, the increased serum expression appears to be linked with several metabolically beneficial effects, reducing the metabolic harm of a High Fat only diet would induce.