Sodium ferrous citrate and 5-aminolevulinic acid improve type 2 diabetes by maintaining muscle and mitochondrial health

Objective Improving mitochondrial function is a promising strategy for intervention in type 2 diabetes mellitus. This study investigated the preventive effects of sodium ferrous citrate (SFC) and 5-aminolevulinic acid phosphate (ALA) on several metabolic dysfunctions associated with obesity because they have been shown to alleviate abnormal glucose metabolism in humans. Methods Six-week-old male C57BL/6J mice were fed with a normal diet, a high-fat diet, or a high-fat diet supplemented with SFC and ALA for 15 weeks. Results The simultaneous supplementation of SFC + ALA to high-fat diet-fed mice prevented loss of muscle mass, improved muscle strength, and reduced obesity and insulin resistance. SFC + ALA prevented abnormalities in mitochondrial morphology and reverted the diet effect on the skeletal muscle transcriptome, including the expression of glucose uptake and mitochondrial oxidative phosphorylation-related genes. In addition, SFC + ALA prevented the decline in mitochondrial DNA copy number by enhancing mitochondrial DNA maintenance and antioxidant transcription activity, both of which are impaired in high-fat diet-fed mice during long-term fasting. Conclusions These findings suggest that SFC + ALA supplementation exerts its preventive effects in type 2 diabetes mellitus via improved skeletal muscle and mitochondrial health, further validating its application as a promising strategy for the prevention of obesity-induced metabolic disorders. Male C57BL/6J mice of 6 weeks of age were fed with a normal diet (Control;10% kcal fat), a high fat diet (HF; 60% kcal fat), or a high fat supplemented with 0.023% w/w sodium ferrous citrate (SFC) and 0.2% w/w 5-aminolevulinic acid phosphate (HF+SFC+ALA) for 15 weeks. Control diet (D12450B) contained 10 kcal% fat, 20 kcal% protein, and 70 kcal% carbohydrate, whereas the HF diet (D12492) contained 60 kcal% fat, 20 kcal% protein, and 20 kcal% carbohydrate (Research Diets, Inc., New Brunswick, NJ, USA). Datas were generated using pooled samples within each group.