Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Intake of the Artificial Sweetener Acesulfame-Potassium Alone and in Combination with a High-Fat Diet Leads to Differential and Sex-Specific Effects on Metabolic Function in Mice

Version 1 : Received: 3 June 2021 / Approved: 8 June 2021 / Online: 8 June 2021 (15:56:03 CEST)

How to cite: Bridge-Comer, P.E.; Vickers, M.H.; Reynolds, C.M. Intake of the Artificial Sweetener Acesulfame-Potassium Alone and in Combination with a High-Fat Diet Leads to Differential and Sex-Specific Effects on Metabolic Function in Mice. Preprints 2021, 2021060239 (doi: 10.20944/preprints202106.0239.v1). Bridge-Comer, P.E.; Vickers, M.H.; Reynolds, C.M. Intake of the Artificial Sweetener Acesulfame-Potassium Alone and in Combination with a High-Fat Diet Leads to Differential and Sex-Specific Effects on Metabolic Function in Mice. Preprints 2021, 2021060239 (doi: 10.20944/preprints202106.0239.v1).

Abstract

Sugar-sweetened beverages are associated with metabolic dysfunction, particularly in those with increased risk factors. Artificial sweeteners (AS) are often promoted as a healthier alternative, yet findings remain conflicting as to their effects on metabolic function. Further, there is a lack of data exploring the interaction between AS and high-fat diets (HFD). We therefore examined the effects of HFD and the AS Acesulfame-potassium (Ace-K) on glucose intolerance and adipose tissue physiology in male and female C57BL/6 mice. 40 mice were randomised to receive either a) a control diet (CDCon; standard control diet/water), b) control diet and Ace-k (CDAS; CD/7.5mM AS in drinking water), c) HFD (HFCon; HFD (45%kcal from fat)/water), or d) HF and AS (HFAS; HFD/7.5mM AS in drinking water) for 6 weeks. A HFD increased body weight in male and female mice independently of AS supplementation. AS induced sex-specific effects protecting against HFD-induced hyperglycaemia and adipocyte hypertrophy in male mice and reducing inflammatory gene expression in the adipose tissue. Conversely in females, AS induced hyperinsulinemia in HFD mice and increased expression of immune-related genes. These findings suggest that supplementation of HFD with AS exacerbates metabolic dysfunction in female mice. This work supports the importance of studying sexually dimorphic responses to an altered nutritional environment and highlights the need for further investigation into the intake of AS, particularly in those already at risk of metabolic disease such as the obese or overweight.

Keywords

adipose tissue; non-nutritive sweeteners; artificial sweeteners; high-fat diet; glucose intolerance

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