Abstract
The pandemic tendency of obesity and its strong association with serious co-morbidities have elicited interest in the underlying mechanisms of these pathologies. Lipid homeostasis, closely involved in obesity, has been reported to be regulated by multiple pathways. mTORC1 is emerging as a critical regulator of lipid metabolism. Here, we describe that the consumption of soy isoflavones, with a structural similarity to that of estradiol, could mitigate obesity through an AKT/mTORC1 pathway. Fed with soy isoflavones, the diet-induced obesity (DIO) male rats exhibited decreased body weight, accompanied with suppressed lipogenesis and adipogenesis, as well as enhanced lipolysis and β‑oxidation. The phosphorylation of AKT and S6 were decreased after soy isoflavone treatment in vivo and in vitro, suggesting an inhibition effect of soy isoflavones on mTORC1 activity. Our study reveals a potential mechanism of soy isoflavones regulating lipid homeostasis, which will be important for obesity treatment.
Highlights
Substantial literature has reported that overweight and obesity are major causes of co-morbidities [1,2], which can lead to further morbidity and mortality caused by diabetes [3,4], fatty liver [5], hypertension [6], cardiovascular diseases [7], and cancer, etc. [8]
The diet-induced obesity (DIO) male rats were randomly divided into the obesity control group (OB, hereafter) fed with the normal diet and the soy isoflavonesgroups fed with both the normal diet and different doses of soy isoflavones
We found that the middle dose of soy isoflavones (MSI, hereafter) and the high dose of soy isoflavones (HIS, hereafter) could significantly reduce the body weight of DIO male rats (Figure 1C), and there was no statistical difference of body weight between the low dose of soy isoflavones group (LSI, hereafter) and the OB group (Figure 1C), which was not consistent with the previous work done with Obese Male Zucker Diabetic Fatty (ZDF) rats [23]
Summary
Substantial literature has reported that overweight and obesity are major causes of co-morbidities [1,2], which can lead to further morbidity and mortality caused by diabetes [3,4], fatty liver [5], hypertension [6], cardiovascular diseases [7], and cancer, etc. [8]. The liver acts as a major organ for fatty acid metabolism, including synthesis, transport, and oxidation processes. The imbalance of these processes may cause excessive fatty acid accumulation, resulting in obesity. MTORC1 is emerging with growing genetic and pharmacological evidence as a central regulator of lipid homeostasis, including lipid synthesis, oxidation, transport, storage, and lipolysis, as well as adipocyte differentiation and function [13]. The activation of mTORC1 is reported to enhance lipogenesis and adipogenesis, resulting in lipid storage [14,15]. Mice lacking mTORC1 activity in their livers, through genetic knockout or specific inhibitors, exhibit lipogenesis defects and enhanced lipolysis and β-oxidation [16,17,18]. The exact mechanisms in these processes are not yet well defined
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