Exercise prehabilitation in lung cancer: Getting stronger to recover faster.

Despite several recent advances, lung cancer surgery is still associated with potentially severe postoperative complications. It has been suggested that preoperative exercise training could render patients with borderline functional parameters eligible for surgery, improve perioperative outcomes and that these benefits might reduce healthcare costs. Nevertheless, given the substantial heterogeneity of the available studies, no specific guidelines for preoperative exercise training have been released so far. This narrative review aims to provide an overview of the potential benefits of exercise training in the preoperative period as a central intervention for lung cancer patients. In detail, the effects of exercise (with different regimens) were evaluated in terms of physical functions, patients' eligibility for curative surgery, postoperative complications and length of stay, with an exploratory focus on healthcare costs and long-term outcomes. Furthermore, a feasible approach for every-day clinical practice is proposed in order to increase the expected benefit deriving from a more extensive and methodical application of prehabilitation exercise, ideally in the context of a comprehensive approach to lung cancer patients, including nutritional and psychological support.

Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats stimulates bioenergetic parameters in liver mitochondria.

The role of 3,5-diiodo-L-thyronine (T2), initially considered only a 3,3',5-triiodo-L-thyronine (T3) catabolite, in the bioenergetic metabolism is of growing interest. In this study we investigated the acute effects (within 1 h) of T2 administration to hypothyroid rats on liver mitochondria fatty acid uptake and ß-oxidation rate, mitochondrial efficiency (by measuring proton leak) and mitochondrial oxidative damage (by determining H2O2 release). Fatty acid uptake into mitochondria was measured assaying carnitine palmitoyl transferase (CPT) I and II activities, and fatty acid ß-oxidation using palmitoyl-CoA as a respiratory substrate. Mitochondrial fatty acid pattern was defined by gas-liquid chromatography. In hypothyroid + T2 vs hypothyroid rats we observed a raise in the serum level of nonesterified fatty acids (NEFA), in the mitochondrial CPT system activity and in the fatty acid ß-oxidation rate. A parallel increase in the respiratory chain activity, mainly from succinate, occurs. When fatty acids are chelated by bovine serum albumin, a T2-induced increase in both state 3 and state 4 respiration is observed, while, when fatty acids are present, mitochondrial uncoupling occurs together with increased proton leak, responsible for mitochondrial thermogenesis. T2 administration decreases mitochondrial oxidative stress as determined by lower H2O2 production. We conclude that in rat liver mitochondria T2 acutely enhances the rate of fatty acid ß-oxidation, and the activity of the downstream respiratory chain. The T2-induced increase in proton leak may contribute to mitochondrial thermogenesis and to the reduction of oxidative stress. Our results strengthen the previously reported ability of T2 to reduce adiposity, dyslipidemia and to prevent liver steatosis.

3,5-Diiodo-L-thyronine administration to hypothyroid rats rapidly enhances fatty acid oxidation rate and bioenergetic parameters in liver cells.

Growing evidence shows that, among triiodothyronine derivatives, 3,5 diiodo-L-thyronine (T(2)) plays an important role in energy metabolism and fat storage. In the present study, short-term effects of T(2) administration to hypothyroid rats on fatty acid oxidation rate and bioenergetic parameters were investigated. Within 1 h following T(2) injection, state 3 and state 4 respiration rates, which were reduced in hypothyroid mitochondria, were noticeably increased particularly in succinate- with respect to glutamate/malate-energized mitochondria. Maximal respiratory activity, observed when glutamate/malate/succinate were simultaneously present in the respiratory medium, was significantly stimulated by T(2) treatment. A T(2)-induced increase in respiratory rates was also observed when palmitoyl-CoA or L-palmitoylcarnitine were used as substrates. No significant change in respiratory control index and ADP/O ratio was observed. The activities of the mitochondrial respiratory chain complexes, especially Complex II, were increased in T(2)-treated rats. In the latter, Complex V activities, assayed in both ATP synthesis and hydrolysis direction, were enhanced. The rate of fatty acid oxidation, followed by conversion of [(14)C]palmitate to CO(2) and ketone bodies, was higher in hepatocytes isolated from T(2)-treated rats. This increase occurs in parallel with the raise in the activity of carnitine palmitoyltransferase-I, the rate limiting enzyme of fatty acid ß-oxidation, assayed in situ in digitonin-permeabilized hepatocytes. Overall, these results indicate that T(2) rapidly increases the ability of mitochondria to import and oxidize fatty acids. An emerging idea in the literature is the ability of T(2) to reduce adiposity and dyslipidemia and to prevent the development in liver steatosis. The results of the present study, showing a rapid T(2)-induced increase in the ability of mitochondria to import and oxidize fatty acids, may contribute to understand the biochemical mechanisms of T(2)-metabolic effects.