High-lard and high-fish-oil diets differ in their effects on function and dynamic behaviour of rat hepatic mitochondria

Background Mitochondria are dynamic organelles that frequently undergo fission and fusion processes, and imbalances in these processes may be involved in obesity and insulin resistance. Aims The present work had the following aims: (a) to evaluate whether the mitochondrial dysfunction present in the hepatic steatosis induced by a high-fat diet is associated with changes in mitochondrial dynamics and morphology; (b) to evaluate whether effects on the above parameters differ between high-lard and high-fish-oil diets, as it has been suggested that fish oil may have anti-obesity and anti-steatotic effects by stimulating fatty acids utilisation. Methods The development of hepatic steatosis and insulin resistance was monitored in rats fed a high-lard or high-fish-oil diet. Immunohistochemical and electronic microscopic observations were performed on liver sections. In isolated liver mitochondria, assessments of fatty acids oxidation rate, proton conductance and oxidative stress (by measuring H2O2 release and aconitase activity) were performed. Western blot and immunohistochemical analyses were performed to evaluate the presence of proteins involved in mitochondrial dynamics (i.e., fusion and fission processes). To investigate the fusion process, mitofusin 2 and autosomal dominant optic atrophy-1 (OPA1) were analysed. To investigate the fission process, the presence of dynamin-related protein 1 (Drp1) and fission 1 protein (Fis1) was assessed. Results High-lard feeding elicited greater hepatic lipid accumulation, insulin resistance with associated mitochondrial dysfunction, greater oxidative stress and a shift towards mitochondrial fission processes (versus high-fish-oil feeding, which had an anti-steatotic effect associated with increased mitochondrial fusion processes). Conclusions Different types of high-fat diets differ in their effect on mitochondrial function and dynamic behaviour, leading to different cellular adaptations to over-feeding

Obesità e steatosi epatica in ratti alimentati con dieta iperlipidica ed ipercalorica

L’obesità è una malattia cronico degenerativa, causata da una combinazione di fattori: ereditari, genetici, metabolici, alimentari, culturali, sociali e psicologici. Quantità eccessive di grasso corporeo costituiscono un pericolo per la salute, soprattutto per il rischio di insorgenza di alcune malattie, quali ipertensione arteriosa, malattie dell’apparato cardiocircolatorio, diabete, osteoporosi, steatosi epatica che nel complesso sono conosciute come sindrome metabolica Un bilancio energetico cronicamente positivo può comportare l’instaurarsi di uno stato di insulino-resistenza prima nel tessuto adiposo, ed in seguito in tutti i tessuti sensibili all’insulina. Se la capacità di espansione degli adipociti è bassa, questi divengono ipertrofici, questa ipertrofia rappresenta una possibile condizione di stress per la cellula, in particolare per il RE, che può attivare pathway metabolici che comportano insulino-resistenza, rilascio di proteine chemoattrattanti dei macrofagi, e se l’infiammazione persiste, la morte dell’adipocita. L’insulino–resistenza degli adipociti, caratterizzata da una bassa capacità liposintetica ed alta capacità lipolitica, causa un aumento in circolo di acidi grassi liberi, questi ultimi si accumulano in maniera ectopica in molti tessuti, tra cui il fegato, comportando lipotossicità ed insulino-resistenza. La disfunzione di alcuni importanti organelli cellulari può essere coinvolta nell’evoluzione della NAFLD (non alcoholic fatty liver disease), gli organelli maggiormente interessati sono il reticolo endoplasmatico ed i mitocondri. Il malfunzionamento del RE provoca la risposta UPR (risposta della proteina non-ripiegata) che è un meccanismo che tende a ripristinare l’omeostasi del RE comportando una condizione di ripresa dell’intera cellula. Se L’UPR fallisce la cellula andrà incontro all’apoptosi e verrà fagocitata dalle cellule di Kupffer ed altri fagociti attivati in situ dal rilascio di citochine. I mitocondri giocano un ruolo importante nel metabolismo della cellula, essendo il principale sito di ossidazione degli acidi grassi e della fosforilazione ossidativa e, al tempo stesso, il più importante sito cellulare di produzione di ROS. L’ eccessiva produzione di specie reattive dell’ossigeno (ROS) è uno dei possibili meccanismi che spiegano la disfunzione mitocondriale che si ritrova nella NAFLD. In queste condizioni si hanno variazioni strutturali e funzionali sia nell’ambito del singolo mitocondrio sia a livello dell’intera rete mitocondriale, in cui i singoli elementi non sono più visti come organelli isolati ma in costante comunicazione fra loro tramite meccanismi di fusione e di fissione mitocondriale

Leptin in lizards: a new metabolic factor?

Leptin is a recently discovered protein implicated in the regulation of food intake, energy expenditure, and whole-body energy balance in rodents and humans. Leptin is indeed characterized by a vast array of functions. Recently, the increasing amount of global research on leptin has shown an unexpected and copious variety of leptin functions, extending from metabolism to reproduction, hematopoiesis, inflammation, and immunological response. The numerous effects of leptin on tissues and endocrine systems have ultimately led to the coordination of whole-body energy metabolism and promoted the expansion of studies on leptin presence and effects in different animal groups, other than humans and rodents. Although studies carried out so far have almost exclusively utilized lizards as animal models, our knowledge in reptiles is still very limited. Such studies provide good evidence for the presence of leptin in target organs such as fat bodies, liver, pancreas, thyroid, stomach, brain, blood, contributing to the definition of a general picture which recalls that of birds and mammals but is also peculiar of these vertebrates. In this review, we summarized the current literature on leptin in lizards and compared it with the recent findings for birds and mammal

Differential Effects of High-Fish Oil and High-Lard Diets on Cells and Cytokines Involved in the Inflammatory Process in Rat Insulin-Sensitive Tissues

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

Differential Effects of High-Fish Oil and High-Lard Diets on Cells and Cytokines Involved in the Inflammatory Process in Rat Insulin-Sensitive Tissues CO-FIRST AUTHOR

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