Combination of Exercise and Intake of Amino Acid Mixture Synergistically Induces Beige Adipocyte Formation in Mice

Abstract

Exercise combined with dietary factors may have significant effects on the suppression of body fat accumulation. Several trials suggest that amino acid mixtures containing alanine, arginine, and phenylalanine (ARF) combined with exercise can significantly reduce body fat accumulation in overweight adults and high-fat diet-induced obesity in mice. We therefore hypothesized that combining ARF and exercise would significantly induce beige adipocyte formation and that this would contribute to reducing body weight, whereas administration of ARF or exercise alone would not. Administration of ARF (1 g/kg body weight, daily) combined with exercise (5 sessions per week) for 4 wk significantly induced formation of beige adipocytes in inguinal white adipose tissue (iWAT) in mice, although ARF or exercise alone did not. Metabolomic analysis showed that plasma lactate concentration was significantly elevated in the exercise1ARF group relative to the exercise group. Furthermore, lactate dehydrogenase B, which increases redox stress by converting lactate to pyruvate in iWAT and triggers induction of uncoupling protein 1 expression was significantly upregulated in iWAT of the exercise1ARF group. These findings demonstrate the unique effect of ARF combined with exercise for inducing beige adipocyte formation, which may be associated with the suggested lactate-mediated pathway. Appropriate mixtures of amino acids could be used as a dietary supplement before exercise and contributed to increasing energy expenditures.

Dietary β-Conglycinin Combined with Exercise Synergistically Induces Beige Adipocyte Formation in Association with Fibroblast Growth Factor 21 Production in Mice

“…As in our previous work, the exercise intensity was increased from 15 m/min in the first week, to 17.5 m/min in the second week, and to 20 m/min in the last 2 weeks. We previously confirmed that the exercise intensity and duration were unable to promote UCP1 expression in BAT and beige adipocyte formation in iWAT . In addition, preliminary experiments indicated that mice fed the 50β-Con diet alone for 4 weeks did not significantly induce beige adipocyte formation.…”

“…Our mice were not fed a high-fat diet and are not a genetic model of obesity. It would be difficult to achieve significantly different results in body weight gain and adipose tissue deposits in C57BL/6 mice fed a normal diet, even if beige adipocyte formation was indeed induced in iWAT. ,, To specifically confirm the effect of exercise + 50β-Con-mediated beige adipocyte formation on fat deposits, the use is required of an animal model of obesity, such as mice fed a high-fat diet. Second, the exact molecular mechanism of the induction of synergistic beige adipocyte formation related to the combination of exercise and a 50β-Con diet needs further clarification.…”

“…The exercise and exercise + 50β-Con group mice were trained for 60 min five times/week for 4 weeks with a level treadmill (LE8710MTS, Panlab-Harvard Apparatus, Cornella, Spain; and KN-73, Natsume Seisakusho Co., Ltd., Tokyo, Japan) . As in our previous work, the exercise intensity was increased from 15 m/min in the first week, to 17.5 m/min in the second week, and to 20 m/min in the last 2 weeks. We previously confirmed that the exercise intensity and duration were unable to promote UCP1 expression in BAT and beige adipocyte formation in iWAT .…”

“…We previously confirmed that the exercise intensity and duration were unable to promote UCP1 expression in BAT and beige adipocyte formation in iWAT. 18 In addition, preliminary experiments indicated that mice fed the 50β-Con diet alone for 4 weeks did not significantly induce beige adipocyte formation. At 16 h after the final exercise training session, a heparin-containing syringe was used to obtain blood samples from isoflurane-anesthetized mice and the blood was centrifuged to isolate plasma.…”

“…14−17 Given the above, dietary factors and exercise may act in concert to promote beige adipocyte formation in WAT, thereby helping to control body weight or conferring additional exercise-related health benefits. We have previously reported that the combined intake of a mixture of amino acids comprising phenylalanine, alanine, and arginine and exercise synergistically induces the development of beige adipocytes in inguinal WAT (iWAT) 18 and that this approach significantly suppresses body fat accumulation in obese humans 19,20 and mice fed a high-fat diet. 21 Accordingly, we hypothesized that the combination of exercise and SP would synergistically promote the formation of beige adipocytes.…”