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Background: There is a myriad of metabolic roles of omega-3 fatty acids. More recently, studies have looked at omega-3 fatty acids effects on skeletal muscle. Objectives: The objective was to determine their effects in situations such as physical activity, obesity, sarcopenia and cachexia. Methods: Bibliographic searches focused on the PubMed database, looking in priority at systematic reviews, until November 2023. Twenty-seven papers were finally included. Results: Omega-3 fatty acids could increase protein anabolism, reduce protein catabolism in the context of exercise-related muscle damages, and could induce beneficial mitochondrial modifications. In obesity, omega-3 fatty acids participate in weight loss and its maintenance, and can help decrease insulin resistance. In sarcopenia atrophic conditions, omega 3 fatty acids allow muscle mass and function maintenance. In cancer cachexia, omega 3 fatty acids are more efficient at the pre-cachectic stage, as they can reduce protein catabolism and increase protein anabolism, but cannot reverse energy imbalance. Conclusions: Omega 3 fatty acids have multiple beneficial effects on skeletal muscle in physical activity, obesity, sarcopenia and cachexia. Yet, these effects are mediated by EPA and DHA, whose sources are solely of marine origins. As marine resources are overexploited, finding diverse sources of omega-3 fatty acids is crucial.

Les acides gras furaniques (FuFAs) sont présents en faible quantité chez les plantes, certains microorganismes et chez les animaux. La biosynthèse des FuFAs chez les plantes et les microorganismes n’est pas complètement décrite. La présence du cycle furane rend les FuFAs très réactifs avec les dérivés réactifs de l’oxygène. Les trois effets biologiques majeurs des FuFAs sont : antioxydant, antimicrobien et anti-inflammatoire. Des études plus spécifiques sur les effets santé ont été menées ces dernières années : les FuFAs et leurs produits de dégradation catabolique (ex. CMPF) pourraient impacter le métabolisme des lipides, l’insulinorésistance et le diabète, les maladies cardiovasculaires, voire certaines maladies neurodégénératives. Les FuFAs pourraient être ainsi des biomarqueurs d’exposition à une alimentation saine, riche en produits de la mer, et également des composés bioactifs de notre alimentation capables de moduler des voies de signalisation avec des effets bénéfiques potentiels contre des désordres métaboliques associés à une alimentation de type occidental.

Natural deep eutectic solvents (NaDES) are new natural solvents in green chemistry that in some cases have been shown to allow better extraction of plant bioactive molecules compared to conventional solvents and higher phenolic compound absorption in rodents. However, there is a serious lack of information regarding their in vivo safety. The purpose of this study was to verify the safety of a NaDES (betaine:glycerol (1:2 mole ratio) of water) extract from green coffee beans, rich in polyphenols. Twelve 6-week-old male Wistar rats were randomized into two groups of 6 animals each and twice daily gavaged for 14 days either with 3 mL of water or 3 mL of phenolic NaDES extract. Oral administration of phenolic NaDES extract induced mortality in two rats. In addition, it induced excessive water consumption, reduced dietary intake and weight loss, hepatomegaly, and plasma oxidative stress associated with high blood lipid levels. In conclusion, this work demonstrated the toxicity of oral administration of the selected NaDES under a short-term condition. This occurs despite the fact that this NaDES extract contains polyphenols, whose beneficial effects have been shown. Therefore, complementary work is needed to find the best dose and formulation of NaDES that are safe for the environment and animals and ultimately for humans.

Les esters d’acides gras hydroxylés (FAHFAs) sont une famille de lipides endogènes récemment découverts par l’équipe du Pr Kahn (Yore et al., 2014). Plusieurs travaux montrent que les FAHFAs améliorent la tolérance au glucose, la sensibilité à l’insuline et sa sécrétion, et possèdent des effets anti-inflammatoires. Les FAHFAs sont présents dans le sang et dans de nombreux tissus chez l’homme et chez le rongeur, mais également dans le lait maternel et dans les aliments. Les FAHFAs sont synthétisés de novo dans les tissus, cependant leurs voies de biosynthèse et de dégradation ne sont pas élucidées à ce jour. Les taux de FAHFAs dans l’organisme seraient modifiés par des altérations physiologiques et physiopathologiques tels le jeûne, l’obésité et l’insulinorésistance. Dans cette revue, nous ferons un bilan sur l’état des connaissances concernant les FAHFAs et présenterons en particulier les effets biologiques de ces lipides bioactifs connus à l’heure actuelle.

Les hormones thyroïdiennes exercent un très grand nombre d'actions physiologiques recouvrant les processus du développement et du métabolisme. La recherche des récepteurs à l'origine de ce large spectre d'influences a conduit à la caractérisation des récepteurs nucléaires de la triiodothyronine (T3) codés par deux gènes c-erbA$\alpha $(TR$\alpha)$et c-erbA$\beta $(TR$\beta )$. Plus récemment, deux formes tronquées de la partie N-terminale du récepteur nucléaire de la T3 TR$\alpha $1, de masse moléculaire 43 et 28 kDa, ont été identifiées dans la mitochondrie. Elles sont synthétisées à partir de l'utilisation de sites d'initiation internes de la traduction présents sur le messager c-erbA$\alpha $1, puis importées dans la mitochondrie selon un processus atypique par rapport aux connaissances actuelles. Deux séquences d'import mitochondrial ont été identifiées dans la partie C-terminale de ces récepteurs ; de plus, leur extrémité N-terminale, dépourvue de charges négatives, joue un rôle permissif dans l'adressage mitochondrial. Alors que la fonction de la p28 reste inconnue, la p43 est un facteur de transcription T3-dépendant du génome mitochondrial qui agit notamment en hétérodimère avec deux autres formes tronquées de récepteurs nucléaires : mtPPAR et mtRXR. L'activation de la p43 par la T3 induit une stimulation de la synthèse protéique mitochondriale, de l'activité de la chaîne respiratoire et de la mitochondriogenèse. Viala signalisation mitochondrie/noyau, cette voie d'action contrôle l'expression de gènes nucléaires impliqués dans la régulation de la prolifération et de la différenciation. En particulier, la surexpression de p43 stimule la différenciation des myoblastes et l'expression de myosine lente en inhibant l'expression de cMyc et en augmentant celles de calcineurine et myogénine. La comparaison des influences respectives des voies d'action nucléaire et mitochondriale de la T3 fait apparaître, selon les effets considérés, une complémentarité (différenciation des myoblastes, mitochondriogenèse), une additivité (différenciation des myoblastes) ou des actions opposées (expression des myosines), induisant ainsi une finesse particulière de la régulation des effets physiologiques de l'hormone.

Le cardiolipide (CL) est un phospholipide exclusivement présent dans la membrane mitochondriale et joue un rôle clé dans plusieurs processus de bioénergétique mitochondriale, ainsi que dans la stabilité et la dynamique de la membrane mitochondriale. En raison de sa richesse en acides gras polyinsaturés (en particulier en acide linoléique), le CL est très sensible à l’attaque par les radicaux libres produits par la mitochondrie. L’oxydation du CL a des conséquences majeures sur le fonctionnement de la mitochondrie, en particulier la phosphorylation oxydative et la production d’ATP. Par ailleurs, les régimes alimentaires plus ou moins riches en graisses peuvent modifier la composition lipidique de la membrane mitochondriale, y compris la teneur en CL et sa composition en acides gras, et ces modifications peuvent par la suite altérer le fonctionnement de la mitochondrie. Or, les régimes alimentaires riches en graisses sont associés à la stéatose hépatique et à l’insulino-résistance, deux problèmes majeurs de santé publique. L’objectif de cet article est de faire le point sur les connaissances actuelles concernant le rôle du CL dans les pathologies nutritionnelles liées à une surcharge en lipides.

In addition to the major fatty acids widely studied, our diet contains many bioactive fatty acids less frequently investigated such as n-3 docosapentaenoic acid (n-3 DPA), natural transfatty acids, conjugated fatty acids (CLAs), furan fatty acids (FuFAs), branched chain fatty acids (BCFAs) and fatty acid esters of hydroxyl fatty acids (FAHFAs). Many of them may have beneficial health effects, particularly in the prevention of cardiovascular diseases, inflammation and metabolic disorders such as diabetes. This review aims to give a brief overview of the current knowledge on these lipids. Thus, information about biosynthesis, food and tissue content, daily intake, biological and potential health effects of these fatty acids is provided.

The importance of mitochondrial activity has recently been extended to the regulation of developmental processes. Numerous pathologies associated with organelle's dysfunctions emphasize their physiological importance. However, regulation of mitochondrial genome transcription, a key element for organelle's function, remains poorly understood. After characterization in the organelle of a truncated form of the triiodothyronine nuclear receptor (p43), a T3‐dependent transcription factor of the mitochondrial genome, our purpose was to search for other mitochondrial receptors involved in the regulation of organelle transcription. We show that a 44 kDa protein related to RXRα (mt‐RXR), another nuclear receptor, is located in the mitochondrial matrix. We found that mt‐RXR is produced after cytosolic or intramitochondrial enzymatic cleavage of the RXRα nuclear receptor. After mitochondrial import and binding to specific sequences of the organelle genome, mt‐RXR induces a ligand‐dependent increase in mitochondrial RNA levels. mt‐RXR physically interacts with p43 and acts alone or through a heterodimerical complex activated by 9‐cis‐retinoic acid and T3 to increase RNA levels. These data indicate that hormonal regulation of mitochondrial transcription occurs through pathways similar to those that take place in the nucleus and open a new way to better understand hormone and vitamin action at the cellular level.—Casas, F., Daury, L., Grandemange, S., Busson, M., Seyer, P., Hatier, R., Carazo, A., Cabello, G., Wrutniak‐Cabello, C. Endocrine regulation of mitochondrial activity: involvement of truncated RXRα and c‐Erb Aαl proteins. FASEB J.17, 426–436 (2003)

Apart from its nuclear pathway, the direct influence of T3 on the cell membrane or mitochondria has already been reported. In this review, the authors present data establishing the existence of a direct T3 mitochondrial pathway and clarify the respective importance of the nuclear and mitochondrial pathways in organelle activity. Numerous studies have reported that, through extranuclear mechanisms, T3 quickly stimulates mitochondrial oxygen consumption and oxidative phosphorylations. The discovery that diiodothyronines (T2) could be a T3 mediator by binding to a subunit of cytochrome-c–oxidase, in conjunction with the characterization of T3 binding sites in the mitochondrial inner membrane, has provided important data for a better understanding of this direct influence. In addition, the discovery that a 43-kD c-ErbA1 protein (p43) acts as a potent T3-dependent mitochondrial transcription factor clarified the rapid influence of the hormone on mitochondrial transcription. This direct pathway is complementary to nuclear stimulation of mitochondrial TFA gene expression. This complementarity is also probably involved in the regulation of mitochondriogenesis requiring coordination between nuclear and mitochondrial transcription. Finally, as other receptors have been recently identified in the organelle, the authors stress that mitochondrial endocrinology could be a new field of research with considerable importance for cell physiology.

Thyroid hormone stimulates myoblast differentiation, through an inhibition of AP-1 activity occurring at the onset of differentiation. In this study we found that the T3 nuclear receptor c-ErbAα1 (T3Rα1) is involved in a mechanism preserving the duration of myoblast proliferation. Independently of the hormone presence, T3Rα1 represses avian MyoD transcriptional activity. Using several mutants of T3Rα1, we found that the hinge region plays a crucial role in the inhibition of MyoD activity. In particular, mutations of two small basic sequences included in α helices abrogate the T3Rα1/MyoD functional interaction. Similarly, the T3 receptor also represses myogenin transcriptional activity. Therefore, despite stimulating avian myoblast differentiation by a T3-dependent pathway not involving myogenic factors, T3Rα1 contributes to maintain an optimal myoblast proliferation period by inhibiting MyoD and myogenin activity.

Thyroid hormone stimulates myoblast differentiation, through an inhibition of AP‐1 activity occurring at the onset of differentiation. In this study we found that the T3 nuclear receptor c‐ErbAα1 (T3Rα1) is involved in a mechanism preserving the duration of myoblast proliferation. Independently of the hormone presence, T3Rα1 represses avian MyoD transcriptional activity. Using several mutants of T3Rα1, we found that the hinge region plays a crucial role in the inhibition of MyoD activity. In particular, mutations of two small basic sequences included in α helices abrogate the T3Rα1/MyoD functional interaction. Similarly, the T3 receptor also represses myogenin transcriptional activity. Therefore, despite stimulating avian myoblast differentiation by a T3‐dependent pathway not involving myogenic factors, T3Rα1 contributes to maintain an optimal myoblast proliferation period by inhibiting MyoD and myogenin activity.

Fenofibrate and fasting are known to regulate several genes involved in lipid metabolism in a similar way. In this study measuring several mitochondrial enzyme activities, we demonstrate that, in contrast to citrate synthase and complex II, cytochrome coxidase (COX) is a specific target of these two treatments. In mouse liver organelles, Western blot experiments indicated that mitochondrial levels of p43, a mitochondrial T3 receptor, and mitochondrial peroxisome proliferator activated receptor (mt‐PPAR), previously described as a dimeric partner of p43 in the organelle, are increased by both fenofibrate and fasting. In addition, in PPARα‐deficient mice, this influence was abolished for mt‐PPAR but not for p43, whereas the increase in COX activity was not altered. These data indicate that: (1) PPARα is involved in specific regulation of mt‐PPAR expression by both treatments; (2) fenofibrate and fasting regulate the mitochondrial levels of p43 and thus affect the efficiency of the direct T3 mitochondrial pathway.

Besides their involvement in the control of nuclear gene expression by activating several peroxisome proliferator‐activated receptors (PPARs), peroxisome proliferators influence mitochondrial activity. By analogy with the previous characterization of a mitochondrial T3 receptor (p43), we searched for the presence of a peroxisome proliferator target in the organelle. Using several antisera raised against different domains of PPARs, we demonstrated by Western blotting, immunoprecipitation and electron microscopy experiments, that a 45 kDa protein related to PPARγ2 (mt‐PPAR) is located in the matrix of rat liver mitochondria. In addition, we found that the amounts of mt‐PPAR are increased by clofibrate treatment. Moreover, in EMSA experiments mt‐PPAR bound to a DR2 sequence located in the mitochondrial D‐loop, by forming a complex with p43. Last, studies of tissue‐specific expression indicated that mt‐PPAR is detected in mitochondria of all tissues tested except the brain in amounts positively related to p43 abundance.

To characterize the regulatory pathways involved in the inhibition of cell differentiation induced by the impairment of mitochondrial activity, we investigated the relationships occurring between organelle activity and myogenesis using an avian myoblast cell line (QM7). The inhibition of mitochondrial translation by chloramphenicol led to a potent block of myoblast differentiation. Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone and oligomycin, which affect the organelle at different levels, exerted a similar influence. In addition, we provided evidence that this phenomenon was not the result of an alteration in cell viability. Conversely, overexpression of the mitochondrial T3 receptor (p43) stimulated organelle activity and strongly potentiated myoblast differentiation. The involvement of mitochondrial activity in an actual regulation of myogenesis is further supported by results demonstrating that the muscle regulatory gene myogenin, in contrast toCMD1(chicken MyoD) and myf5, is a specific transcriptional target of mitochondrial activity. Whereas myogenin mRNA and protein levels were down-regulated by chloramphenicol treatment, they were up-regulated by p43 overexpression, in a positive relationship with the expression level of the transgene. We also found that myogenin or CMD1 overexpression in chloramphenicol-treated myoblasts did not restore differentiation, thus indicating that an alteration in mitochondrial activity interferes with the ability of myogenic factors to induce terminal differentiation.

The product of the B-cell translocation gene 1 (BTG1), a member of an antiproliferative protein family including Tis-21/PC3 and Tob, is thought to play an important role in the regulation of cell cycle progression. We have shown in a previous work that triiodothyronine (T3) stimulates quail myoblast differentiation, partly through a cAMP-dependent mechanism involved in the stimulation of cell cycle withdrawal. Furthermore, we found that T3 or 8-Br-cAMP increases BTG1 nuclear accumulation in confluent myoblast cultures. In this study, we report that BTG1 is essentially expressed at cell confluence and in differentiated myotubes. Whereas neither T3 nor cAMP exerted a direct transcriptional control upon BTG1 expression, we found that AP-1 activity, a crucial target involved in the triiodothyronine myogenic influence, repressed BTG1 expression, thus probably explaining the low BTG1 expression level in proliferating myoblasts. In transient transfection studies, we demonstrated that an AP-1-like sequence located in the BTG1 promoter was involved in this negative regulation. Our present data also bring evidence that the stimulation of BTG1 nuclear accumulation by T3 or 8-Br-cAMP probably results from an increased nuclear import or retention in the nucleus. Lastly, BTG1 overexpression in quail myoblasts mimicked the T3 or 8-Br-cAMP myogenic influence: (i) inhibition of myoblast proliferation due to an increased rate of myoblast withdrawal from the cell cycle; and (ii) stimulation of terminal differentiation. These data suggest that BTG1 is probably involved in T3 and cAMP myogenic influences. In conclusion, BTG1 is a T3 target involved in the regulation of myoblast differentiation.

In earlier research, we identified a 43-kDa c-ErbAα1 protein (p43) in the mitochondrial matrix of rat liver. In the present work, binding experiments indicate that p43 displays an affinity for triiodothyronine (T3) similar to that of the T3 nuclear receptor. Using in organello import experiments, we found that p43 is targeted to the organelle by an unusual process similar to that previously reported for MTF1, a yeast mitochondrial transcription factor. DNA-binding experiments demonstrated that p43 specifically binds to four mitochondrial DNA sequences with a high similarity to nuclear T3 response elements (mt-T3REs). Using in organello transcription experiments, we observed that p43 increases the levels of both precursor and mature mitochondrial transcripts and the ratio of mRNA to rRNA in a T3-dependent manner. These events lead to stimulation of mitochondrial protein synthesis. In transient-transfection assays with reporter genes driven by the mitochondrial D loop or two mt-T3REs located in the D loop, p43 stimulated reporter gene activity only in the presence of T3. All these effects were abolished by deletion of the DNA-binding domain of p43. Finally, p43 overexpression in QM7 cells increased the levels of mitochondrial mRNAs, thus indicating that the in organello influence of p43 was physiologically relevant. These data reveal a novel hormonal pathway functioning within the mitochondrion, involving a truncated form of a nuclear receptor acting as a potent mitochondrial T3-dependent transcription factor.

Parents and educators concerned with the quality of education in Canadian schools have been subjected to a concerted campaign (through editorials, columns, and letters to the editor in major dailies and magazines, as well as a spate of books with alarmist titles) aimed at convincing them that the lack of adequate testing represents a major shortcoming and a stumbling block to educational reform. Provincewide and nationwide standardized achievement tests are offered as an indispensable tool to understand what works and what does not, to let parents know how schools are doing and how well their children are performing, and to make teachers and school boards accountable. Provincial education authorities are finding it increasingly difficult to resist the pressure, with Ontario the latest to jump on the testing bandwagon. However, although concerns about school curricula and about the best methods for testing student learning and performance are legitimate, the belief that standardized achievement tests are part of the solution to many ills allegedly afflicting our educational system does not stand up to the increasingly clear evidence of the many problems associated with the construction and administration of these tests, as well as the misuse and abuse of test scores. Far from being a panacea, this approach has proved to be fraught with dangers and adverse effects, from a narrowing of the curriculum to overemphasis of routine processes at the expense of higher learning skills, with virtually no empirical support for the purported benefits. With Canadian students facing the risk of being subjected to the same abuses as their U.S. counterparts, this paper reviews recent contributions and attempts to alert educators and policymakers to the serious deficiencies of this type of testing.

Technological innovations improve the welfare of a country facing fixed terms of trade, but may lead to immiserization when the terms of terms of trade are adversely affected. This paper establishes that transport innovation can be immiserizing for a small country when the transport sector exhibits variable returns to scale. The release of resources from the transport sector triggers Rybczynski-like effects, and the resulting expansion (contraction) in the volume of trade and in the demand for transport services raises unit costs of these services, and may reduce welfare in the presence of decreasing (increasing) returns to scale. [411]

We have previously shown that c-Erb A and v-Erb A display a cell-specific activity in avian myoblasts. In this work, we have compared the molecular basis of thyroid hormone action in HeLa cells and in QM7 myoblasts. The transcriptional activity of c-Erb Aα1 through a palindromic thyroid hormone response element (TRE) was similar in both cell types. However, c-Erb A did not activate gene transcription through a direct repeat sequence (DR) 4 TRE in myoblasts in contrast to results obtained in HeLa cells. Moreover, whereas retinoic acid receptor-AP-1 interactions were functional in both cell types, thyroid hormone receptor (T3R)-AP-1 interactions were only functional in HeLa cells. Using electrophoretic mobility shift assays, functional tests, and Northern blot experiments, we observed that RXR isoforms are not expressed in proliferating myoblasts. Expression of RXR γ in these cells did not influence T3R transcriptional activity through a palindromic TRE but induced such an activity through a DR4 TRE. Moreover, it restored c-Erb A-AP-1 functionality in QM7 myoblasts and enhanced the myogenic influence of T3. We also observed that c-Jun overexpression in proliferating QM7 cells restored T3R transcriptional activity through a DR4 TRE. Therefore, alternative mechanisms are involved in the induction of T3R transcriptional activity according to the cell status (proliferation: c-Jun; differentiation: RXR). In addition we provide the first evidence that RXR is required to allow inhibition of AP-1 activity by ligand-activated T3R. Lastly, we demonstrate the importance of RXR in the regulation of myoblast differentiation by T3.