doi: 10.3967/bes2023.134
Exposure to Electromagnetic Fields from Mobile Phones and Fructose consumption Coalesce to Perturb Metabolic Regulators AMPK/SIRT1-UCP2/FOXO1 in Growing Rats
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Abstract:
Objective In this study, the combined effect of two stressors, namely, electromagnetic fields (EMFs) from mobile phones and fructose consumption, on hypothalamic and hepatic master metabolic regulators of the AMPK/SIRT1-UCP2/FOXO1 pathway were elucidated to delineate the underlying molecular mechanisms of insulin resistance. Methods Weaned Wistar rats (28 days old) were divided into 4 groups: Normal, Exposure Only (ExpO), Fructose Only (FruO), and Exposure and Fructose (EF). Each group was provided standard laboratory chow ad libitum for 8 weeks. Additionally, the control groups, namely, the Normal and FruO groups, had unrestricted access to drinking water and fructose solution (15%), respectively. Furthermore, the respective treatment groups, namely, the ExpO and EF groups, received EMF exposure (1,760 MHz, 2 h/day x 8 weeks). In early adulthood, mitochondrial function, insulin receptor signaling, and oxidative stress signals in hypothalamic and hepatic tissues were assessed using western blotting and biochemical analysis. Result In the hypothalamic tissue of EF, SIRT1, FOXO 1, p-PI3K, p-AKT, Complex III, UCP2, MnSOD, and catalase expressions and OXPHOS and GSH activities were significantly decreased (P < 0.05) compared to the Normal, ExpO, and FruO groups. In hepatic tissue of EF, the p-AMPKα, SIRT1, FOXO1, IRS1, p-PI3K, Complex I, II, III, IV, V, UCP2, and MnSOD expressions and the activity of OXPHOS, SOD, catalase, and GSH were significantly reduced compared to the Normal group (P < 0.05). Conclusion The findings suggest that the combination of EMF exposure and fructose consumption during childhood and adolescence in Wistar rats disrupts the closely interlinked and multi-regulated crosstalk of insulin receptor signals, mitochondrial OXPHOS, and the antioxidant defense system in the hypothalamus and liver. -
Key words:
- EMF-mobile phone /
- Fructose /
- Childhood-adolescence /
- Insulin receptor signal /
- Mitochondrial OXPHOS /
- Antioxidant system /
- Hypothalamic insulin resistance /
- Hepatic insulin resistance
The authors declare no conflicts of interest.
注释:1) AUTHOR CONTRIBUTIONS: 2) CONFLICTS OF INTEREST: -
Figure 1. Effect of EMF and fructose consumption in childhood-adolescence perturbed the hypothalamic master regulator protein of mitochondrial and insulin functions and skews hypothalamic transmitting insulin signaling via PI3K/AKT by early adulthood. (A) Metabolic key regulator protein p-AMPKα remained unaffected in EF, and (B) SIRT1 was significantly reduced in EF. (C) Expression of the insulin function regulator protein-FOXO-1 was markedly reduced in EF. (D) Hypothalamic expression of signaling adapter protein IRS1 was significantly reduced in ExpO and FruO. (E) Transducer protein PI3K expression was significantly reduced in EF. (F) Expression of the protein p-AKT was significantly reduced in EF and (G) AKT was unchanged. Thus, this shows hypothalamic PI3K/AKT signaling is impaired to attenuate the insulin signaling in response to glucose metabolism and energy regulation.
Figure 2. Effect of EMF and fructose consumption in childhood-adolescence interrupt hypothalamic mitochondrial oxidative phosphorylation (OXPHOS) system in ATP production and skews antioxidant defensive system by early adulthood. (A) Hypothalamic expression of Complex III was significantly reduced in EF. (B) and (C) Expression of protein Complex IV was significantly reduced in FurO and Complex V was unchanged in EF. (D) The activity of Complex I was significantly reduced in EF. (E, F, and G) Activity of Complex II, Complex IV, and Complex V was markedly reduced in EF. (H) Hypothalamic UCP2 expression, an ROS regulator, was significantly reduced in EF. (I) Expression of MnSOD, a ROS regulator, was significantly reduced in EF. (J) Expression of Catalase, which protects from ROS-induced oxidative damage, was significantly reduced in EF. (K, L, and M) Activity of SOD, catalase, and GSH was significantly reduced in EF.
Figure 3. Effects of EMF and fructose consumption during childhood and adolescence on hepatic master regulator proteins of mitochondrial and insulin function and impairment of hepatic insulin signaling via PI3K/AKT in early adulthood. (A) Metabolic key regulator protein p-AMPKα was significantly increased in EF and (B) SIRT1 was significantly reduced in EF. (C) Expression of the transcription factor mediator of insulin function and mitochondrial OXPHOS. FOXO-1 was markedly reduced in EF. (D) Hepatic signaling adapter protein IRS1 was significantly reduced in FruO and EF. (E) Expression of transducer protein p-PI3K was significantly reduced in FruO and EF. (F) Expression of the protein p-AKT was significantly reduced in ExpO and FruO. (G) AKT was unchanged in EF.
Figure 4. Effect of EMF and fructose consumption in childhood-adolescence interrupt hepatic mitochondrial oxidative phosphorylation (OXPHOS) Complex (I–V) in ATP production and skews the hepatic antioxidant defensive system by early adulthood. (A–B) Hepatic expression of Complex II and Complex III was significantly reduced in ExpO, FruO, and EF. (C–D) Expression of protein Complex IV and Complex V was significantly reduced in EF. (E, F, G, and H) Activity of Complex I, Complex II, Complex IV, and Complex V was markedly reduced in EF. (E) Hepatic expression of UCP2, a ROS regulator, was significantly reduced in EF (I) Expression of MnSOD, a ROS regulator, was significantly reduced in ExpO, FruO, and EF. (J) Expression of Catalase, which protects from ROS-induced oxidative damage, was significantly unchanged in EF. (K) Expression of Catalase was significantly reduced in EF. (L, M, and N) Activity of SOD, catalase, and GSH was significantly reduced in EF.
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