Mitigating the Impact of High-Fat Diet: The Role of Metformin and Exercise Interventions in Alleviating Autism-Like Behaviors and Insulin Resistance in Mice

Abstract

The rising consumption of high-fat foods in contemporary society has been linked to the emergence of autism-like behaviors and increased insulin resistance. This study sought to examine the effects of metformin (MET) treatment and two forms of aerobic exercise—moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT)—on ameliorating autism-like behaviors and insulin resistance caused by a high-fat diet (HFD). Fifty male mice were divided into a normal diet (ND, n = 10) and HFD (n = 40) groups, with the latter subjected to an 8-week HFD regimen. The HFD group was subsequently divided into HFD + Veh, HFD + MET, HFD + MICT, and HFD + HIIT subgroups, receiving MET treatment and treadmill training for 8 weeks. Results revealed that HFD consumption led to increased anxiety-like behaviors (P < 0.05) and peripheral insulin resistance (P < 0.0001) compared to the ND group. In addition, there was a rise in autism-like behaviors in the HFD + Veh subgroup (P < 0.0001). MET and HIIT interventions demonstrated positive effects in reducing autism-like behaviors (P < 0.05), while both HIIT (P < 0.0001) and MICT (P < 0.05) effectively reduced anxiety levels. Furthermore, MET (P < 0.05), MICT (P < 0.05) and HIIT (P < 0.0001) interventions successfully lowered peripheral insulin resistance. This study highlights the negative impact of HFD consumption on social interactions and anxiety levels, with MET, MICT, and HIIT interventions exhibiting varying degrees of effectiveness in mitigating these adverse effects. Particularly, HIIT showed promise in addressing both HFD-induced behavioral and metabolic conditions. These findings offer crucial insights into potential therapeutic strategies for combating the harmful effects of HFD on behavior and metabolism.

Keywords

High-fat diet / Autism behavior / Insulin resistance / Metformin / Training / Mouse

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Beijing Sport University