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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.

Environmental chemicals can be introduced by consuming contaminated foods. The environmental chemical dichlorodiphenyldichloroethylene (DDE), a persistent metabolite of dichlorodiphenyltrichloroethane (DDT), can affect spermatogenesis. Our study aims to evaluate, by using spectrophotometric analyses, western blot, and immunohistochemistry, the adaptive responses in testis of adult rats treated with a non-toxic dose of DDE, alone or in association with a high-fat diet (HFD). Four experimental groups were performed: N (normal diet), D (HFD), D + DDE (HFD + DDE), N + DDE (normal diet + DDE). D group showed a reduction in antioxidant capacity, and increases in lipid peroxidation, apoptosis, and proliferation associated with morphological impairment. A reduction in androgen receptor (AR) and serum testosterone levels were also found. DDE-treated groups exhibited higher lipid peroxidation levels compared to N and D, associated with pronounced defect in antioxidant capacity, apoptosis, cellular proliferation, as well as with tissue damage. Moreover, decreases in AR and serum testosterone levels were found in DDE-treated groups vs. N and D. In conclusion, HFD and DDE produced cellular stress leading to antioxidant impairment, apoptosis, and decreases in AR and serum testosterone levels associated with tissue damage. Cellular proliferation could be used as an adaptation to counterbalance the occurred damage, maintaining a pool of tubules that follow physiological maturation.

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.

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress have been suggested to play a key role in insulin resistance development. Reactive oxygen species (ROS) production and lipid accumulation due to mitochondrial dysfunction seemed to be important mechanisms leading to cellular insulin resistance. Moreover, mitochondria are functionally and structurally linked to ER, which undergoes stress in conditions of chronic overnutrition, activating the unfolded protein response, which in turn activates the principal inflammatory pathways that impair insulin action. Among the nutrients, dietary fats are believed to play key roles in insulin resistance onset. However, not all dietary fats exert the same effects on cellular energy metabolism. Dietary omega 3 polyunsaturated fatty acids (PUFA) have been suggested to counteract insulin resistance development by modulating mitochondrial bioenergetics and ER stress. In the current review, we summarized current knowledge on the role played by mitochondrial and ER stress in inflammation and insulin resistance onset, focusing on the modulation role of omega 3 PUFA on these stress pathways. Understanding the mechanisms by which omega 3 PUFA modulates cellular metabolism and insulin resistance in peripheral tissues may provide additional details on the potential impact of omega 3 PUFA on metabolic function and the management of insulin resistance in humans.

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.

In our modern society, exposure to stressful environmental stimuli, such as pollutants and/or chronic high-fat feeding, continuously induce tissular/organ metabolic adaptation to promote cellular survival. In extreme conditions, cellular death and tissular/organ damage occur. Mitochondria, as a cellular energy source, seem to play an important role in facing cellular stress induced by these environmental stimuli. On the other hand, mitochondrial dysfunction and oxidative stress play a key role in environmental stress-induced metabolic diseases. However, little is known about the combined effect of simultaneous exposure to chronic high-fat feeding and environmental pollutants on metabolic alterations at a tissular and cellular level, including mitochondrial dysfunction and oxidative stress induction. Our research group recently addressed this topic by analysing the effect of chronic exposure to a non-toxic dose of the environmental pollutant dichlorodiphenyldichloroethylene (DDE) associated with high-fat feeding in male Wistar rats. In this review, we mainly summarize our recent findings on mitochondrial adaptive response and oxidative stress induction in the liver, the main tissue involved in fat metabolism and pollutant detoxification, and in male gonads, the main targets of endocrine disruption induced by both high-fat feeding and environmental pollutants.

Oxidative stress plays a key role in steatohepatitis induced by both xenobiotic agents and high fat diet (HFD). The present study aimed to evaluate hepatic oxidative stress and anti- oxidant systems response in rats exposed to HFD and/or non-toxic dose of dichlorodiphe- nyldichloroethylene (DDE), the first metabolite of dichlorodiphenyltrichloroethane. Groups of 8 rats were so treated for 4 weeks: 1- standard diet (N group); 2- standard diet plus DDE (10 mg/kg b.w.) (N+DDE group); 3- HFD (D group); 4- HFD plus DDE (D+DDE group). Oxi- dative stress was analyzed by determining malondialdehyde as lipid peroxidation product, while the anti-oxidant systems were evaluating by measuring the levels of the principal cyto- solic and mitochondrial antioxidant proteins and enzymes, namely superoxide dismutase 1 and 2 (SOD1, SOD2), glutathione peroxidase 1 (GPx1) and uncoupling protein 2 (UCP2) involved in the control of hepatic reactive oxygens species (ROS) accumulation. The results showed malondialdehyde accumulation in livers of all groups, confirming the pro-oxidant effects of both HFD and DDE, but with a greater effect of DDE in absence of HFD. In addi- tion, we found different levels of the analyzed anti-oxidant systems in the different groups. DDE mainly induced UCP2 and SOD2, while HFD mainly induced GPx1. Noteworthy, in the condition of simultaneous exposure to DDE and HFD, the anti-oxidant response was more similar to the one induced by HFD than to the response induced by DDE. Present findings confirmed that both HFD and xenobiotic exposure induced hepatic oxidative stress and showed that the anti-oxidant defense response was not the same in the diverse groups, sug- gesting that UCP2 induction could be an adaptive response to limit excessive ROS damage, mainly in condition of xenobiotic exposure.

OBJECTIVES:Omega (ω)-3 polyunsaturated fatty acids (PUFA) are dietary compounds able to attenuate insulin resistance. Anyway, the precise actions of ω-3PUFAs in skeletal muscle are overlooked. We hypothesized that PUFAs, modulating mitochondrial function and efficiency, would ameliorate pro-inflammatory and pro-oxidant signs of nutritionally induced obesity. STUDY DESIGN:To this aim, rats were fed a control diet (CD) or isocaloric high fat diets containing either ω-3 PUFA (FD) or lard (LD) for 6 weeks. RESULTS:FD rats showed lower weight, lipid gain and energy efficiency compared to LD-fed animals, showing higher energy expenditure and O2 consumption/CO2 production. Serum lipid profile and pro-inflammatory parameters in FD-fed animals were reduced compared to LD. Accordingly, FD rats exhibited a higher glucose tolerance revealed by an improved glucose and insulin tolerance tests compared to LD, accompanied by a restoration of insulin signalling in skeletal muscle. PUFAs increased lipid oxidation and reduced energy efficiency in subsarcolemmal mitochondria, and increase AMPK activation, reducing both endoplasmic reticulum and oxidative stress. Increased mitochondrial respiration was related to an increased mitochondriogenesis in FD skeletal muscle, as shown by the increase in PGC1-α and -β. CONCLUSIONS:our data strengthened the association of high dietary ω3-PUFA intake with reduced mitochondrial energy efficiency in the skeletal muscle.

Diet induced obesity is associated with impaired mitochondrial function and dynamic behavior. Mitochondria are highly dynamic organelles and the balance in fusion/fission is strictly associated with their bioenergetics. Fusion processes are associated with the optimization of mitochondrial function, whereas fission processes are associated with the removal of damaged mitochondria. In diet-induced obesity, impaired mitochondrial function and increased fission processes were found in liver and skeletal muscle. Diverse dietary fat sources differently affect mitochondrial dynamics and bioenergetics. In contrast to saturated fatty acids, omega 3 polyunsaturated fatty acids induce fusion processes and improve mitochondrial function. Moreover, the pro-longevity effect of caloric restriction has been correlated with changes in mitochondrial dynamics leading to decreased cell oxidative injury. Noteworthy, emerging findings revealed an important role for mitochondrial dynamics within neuronal populations involved in central regulation of body energy balance. In conclusion, mitochondrial dynamic processes with their strict interconnection with mitochondrial bioenergetics are involved in energy balance and diet impact on metabolic tissues.

The endocrine islets of Triturus carnifex consisted mainly of a core of B cells and a peripheral mantle of A cells. A rich supply of nerve terminals innervated the endocrine cells. The A and B cells showed a cytoplasm filled with secretory granules, glycogen, lipid droplets, microtubules and microfilaments, a well‐developed RER, and Golgi. To study the hormonal control of the secretion and the eventual morphological changes of the cells evoked by the hormonal stimulus, the newts were treated with 100 and 3×100 ug of epinephrine that caused dose‐dependent variations in pancreatic endocrine cells. B cells were inhibited by the lowest and stimulated by the highest doses, whereas A cells were always stimulated.

In early spring, neuropeptide Y injections in the lizard Podarcis s. sicula caused an increase of appetite in animals compared with those injected with saline alone. Glycemia determination showed an annual cycle with a maximum of blood glucose in summer when animals feed, and a minimum in winter when they undergo a semi‐hibernation period during which they do not eat. In NPY‐treated lizards, blood glucose dropped as the NPY dose increased to reach significantly lower values than those of controls fed for the whole time of treatment. Both endocrine and exocrine pancreas was affected by the treatment. In particular, the insulin immunoreactive B cells appeared less intensely immunostained than those of the controls, with a progressive reduction of immunostaining, according to the NPY doses used. Optical density of immunostaining measurements of B cells, showing a progressive reduction of this parameter in the treated lizards, supported the morphological observations. Acinar cells, too, exhibited red...

In the endocrine pancreas of eight species of Chalcides four types of endocrine cells (designated A, B, D, and PP or F) were revealed by immunocytochemical methods. A cells were immunoreactive to anti‐glucagon serum: B cells to anti‐insulin serum; D cells to anti‐somatostatin serum; PP cells to anti‐pancreatic polypeptide serum. In the splenic lobe, where endocrine cells are mainly concentrated and form large insular masses, A cells represent the most abundant type and PP cells are very rare or absent. In the ventral lobe, con taining small endocrine islets, all four endocrine types are present. However A, B, and D cells are preferentially located in the median region, while PP cells are numerous in the lateral region, where they appear isolated or associated in small groups scattered in the exocrine parenchyma. It was suggested that this regional distribution of the endocrine cell types reflects the different em bryonic origin of the two pancreatic lobes and/or different cell fun ctions.

Introduction: High-fat feeding induces hepatic lipid accumulation associated with concomitant mitochondrial fat oxidation enhancement and electron-chain impairment that result in excessive formation of reactive oxygen species. Little is known about hepatic mitochondrial dynamic behaviours adaptation to high-fat feeding. Mitochondria are dynamic organelles that frequently undergo fission and fusion processes, imbalances in which have recently emerged as important etiological factors in obesity and insulin-resistance. Bearing in mind that fish-oil feeding has anti-steatotic effects, the present work aimed to evaluate the effects of high-lard (mainly saturated fatty acids) and high-fish-oil (mainly omega-3 polyunsaturated fatty acids) diets on both hepatic mitochondrial bioenergetic and dynamic behaviour. Methods: Hepatic lipid accumulation was monitored in rats fed a high-lard or high-fish-oil (40% J/J) diet for 6 weeks. Mitochondrial functions were assessed by evaluating FADH2 linked respiratory rates, fatty acid oxidation rates, energetic efficiency (by measuring basal and fatty acid induced proton leak kinetics), and oxidative stress (by measuring H2O2 release and aconitase activity). Mitochondrial dynamics behaviour was assessed by analysing the proteins relevant to the processes of fusion (MFN2, OPA1) and fission (DRP1, Fis1) (by western blot and immunohistochemical analysis). Results: Hepatic lipid accumulation, electron chain impairment and oxidative stress induced by high-lard diet were associated with both decreased fatty acid induced proton leak and a shift toward mitochondrial fission processes (decreased MFN2 content and increased DRP1 and Fis1 content). On the other hand, the anti-steatotic effect of high-fish oil feeding was associated with mild uncoupling (increases in both basal and fatty acid induced proton leak kinetics), oxidative stress prevention and increased mitochondrial fusion processes. Conclusions: Fission phenotype and increased energetic efficiency are associated with the steatotic effect of high-lard diet, whereas fusion phenotype and decreased energetic efficiency contributed to the anti-steatotic effect of high-fish oil diet.

Morphological changes are reported in the endocrine pancreas of the lizard Podarcis s. sicula after insulin and ACTH administration. After short term insulin administration both A and B cells appeared hypertrophic and stored large quantities of secretory granules. Chronic insulin administration led instead to a progressive degranulation of both kinds of insular cells, mainly with the A cells. During ACTH administration, B cells showed progressive degranulation while A cells remained almost completely unaffected. The possible mechanisms of pancreatic hormone release after insulin and ACTH administration are discussed.

The authors have studied the effects of insulin and glucagon administration on the blood glucose levels of the lizard Podarcis s. sicula Raf. during the winter. The administration of insulin induces hypoglycaemia with the blood glucose levels reaching a minimum after 3 injections of 4 IU of insulin and a subsequent partial recovery during the course of the treatment. Glucagon treatment on the contrary causes a strong hyperglycaemia which is dose‐dependent and reaches the maximum values about 2.30 hours after the administration of the hormone. The hyperglycaemic action of glucagon is evident also in specimens previously treated with insulin. The glucagon action is not long lasting and the blood glucose levels become normal within 24 hours of the administration of glucagon.