**5. Conclusions**

In conclusion, our research confirmed the literature on HFD and DDE e ffects in terms of oxidative stress associated with changes in lipid metabolism, mainly in the liver.

Hepatic adaptations to dietary fats and pesticides induced a general control of hepatic injury in which mitochondrial function and cellular metabolism were directly involved. Antioxidant system stimulation and mitochondrial UCP2 up-regulation seemed to play a potential protective role in counteracting ROS overproduction, mainly in the presence of environmental pollutants.

In the testis, HFD altered the oxidative balance and induced lipotoxicity, cellular death and apoptosis. On the other hand, DDE generated the highest tissular alterations and dysfunctions with impairment of spermatogenesis under the conditions of both individual or simultaneous exposure to pesticide and dietary fats, with a worse redox state when pesticide exposure was not associated with a high fat consumption.

With the limitation that further studies are needed to better identify the mitochondrial role in response to environmental stimuli, such as pollutants and chronic high-fat feeding, our experimental research summarized in the present review was the first to address the topic of mitochondrial and oxidative stress responses to chronic simultaneous exposure to both environmental stimuli in di fferent organs. Given that, in modern obesogenic society, we are frequently exposed to both a high-fat diet and several environmental pollutants with consequently increased risks of related metabolic disease, studies on mitochondrial involvement in the cellular response to these environmental stimuli can be useful in understanding the adaptive mitochondrial response required to maintain a healthy condition and, therefore, to target mitochondria in the prevention and therapy of environmental stimuli-induced metabolic diseases.

**Funding:** This work was supported by University of Salerno (Fondi FARB 2018, 300389FRB18LIONE).

**Conflicts of Interest:** The authors declare no conflict of interest.
