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High-fat diets rich in fish oil (HFO diet, mainly &omega, 3-PUFAs), in contrast to high-fat diets rich in lard (HL diet, mainly saturated fatty acids) have been shown to induce improvement in mitochondrial function and fusion processes associated with a reduction in reactive oxygen species production in both liver and skeletal muscle. High-fat diets may also impair testicular function, and mitochondria represent important cellular organelles with a pivotal role in reproductive function. Mitochondria are dynamic organelles that frequently undergo fission/fusion processes. A shift toward mitochondrial fusion process has been associated with improvement of mitochondrial function, as well as with &omega, 3-PUFAs protective effects. The present study aimed to analyze the effect of chronic overfeeding (six weeks) with HFO or HL diet on testicular tissue histology, oxidative stress, antioxidant defenses, and mitochondrial fusion (mitofusin 2) and fission (dynamic related protein 1) protein. Our results showed that HFO diet induced less testicular histology impairment, oxidative stress, and apoptosis compared to a HL diet. This finding was associated with an increase in antioxidant activities and a shift toward mitochondrial fusion processes induced by HFO diet compared to HL diet, suggesting that &omega, 3-PUFAs may act as bioactive compound targeting mitochondria dynamics to prevent testicular impairment.

The growing number of studies on metallothioneins (MTs), cysteine-rich metal-binding proteins, have been disclosing new functions of these proteins. Thanks to their inducibility, they were considered to play a pivotal role in regulating trace metals homeostasis and in detoxification from heavy metals; nowadays, it is known that they are involved in various physiological and pathological processes, such as regulation of apoptosis, elimination of free radicals, and protection of nucleic acids against toxic insults. MT induction has been demonstrated following stress factors other than heavy metals, such as endocrine-disrupting chemicals, insecticides, and herbicides. However, retrieved data are often controversial: in some cases, xenobiotics elicit MT expression and synthesis; under different conditions, they lead to a decrease in cellular MT content. This review describes the MT response to dichlorodiphenyltrichloroethane (DDT) contamination in mammalian tissues. In particular, attention focuses on changes in MT expression, synthesis, and localization in rat liver, kidneys, and testes following oral administration of dichlorodiphenyldichloroethylene (DDE), the main metabolite of DDT, under normal dietary conditions or in combination with a high fat diet potentially able to increase the cellular uptake of this lipophilic pesticide. The potential connection between MT expression and synthesis, lipophilic substances and trace metals availability is also discussed.

Dietary fat sources may differentially affect the development of inflammation in insulin-sensitive tissues during chronic overfeeding. Considering the anti-inflammatory properties of ω-3 fatty acids, this study aimed to compare the effects of chronic high-fish oil and high-lard diets on obesity-related inflammation by evaluating serum and tissue adipokine levels and histological features in insulin-sensitive tissues (white adipose tissue, skeletal muscle and liver). As expected, a high-lard diet induced systemic and peripheral inflammation and insulin resistance. Conversely, compared with a high-lard diet, a high-fish oil diet resulted in a lower degree of systemic inflammation and insulin resistance that were associated with a lower adipocyte diameter as well as lower immunoreactivity for transforming growth factor β 1 (TGFβ1) in white adipose tissue. A high-fish oil diet also resulted in a lower ectopic lipid depot, inflammation degree and insulin resistance in the skeletal muscle and liver. Moreover, a high-fish oil diet attenuated hepatic stellate cell activation and fibrogenesis in the liver, as indicated by the smooth muscle α-actin (α-SMA) and TGFβ1 levels. The replacement of lard (saturated fatty acids) with fish oil (ω-3 fatty acids) in chronic high-fat feeding attenuated the development of systemic and tissue inflammation.