Mitochondrial efficiency and insulin resistance

Insulin resistance, “a relative impairment in the ability of insulin to exert its effects on glucose, protein and lipid metabolism in target tissues,” has many detrimental effects on metabolism and is strongly correlated to deposition of lipids in non-adipose tissues. Mitochondria are the main cellular sites devoted to ATP production and fatty acid oxidation. Therefore, a role for mitochondrial dysfunction in the onset of skeletal muscle insulin resistance has been proposed and many studies have dealt with possible alteration in mitochondrial function in obesity and diabetes, both in humans and animal models. Data reporting evidence of mitochondrial dysfunction in type two diabetes mellitus are numerous, even though the issue that this reduced mitochondrial function is causal in the development of the disease is not yet solved, also because a variety of parameters have been used in the studies carried out on this subject. By assessing the alterations in mitochondrial efficiency as well as the impact of this parameter on metabolic homeostasis of skeletal muscle cells, we have obtained results that allow us to suggest that an increase in mitochondrial efficiency precedes and therefore can contribute to the development of high-fat-induced insulin resistance in skeletal muscle

A possible link between hepatic mitochondrial dysfunction and diet-induced insulin resistance

Mitochondria are the main cellular sites devoted to ATP production and lipid oxidation. Therefore, the mitochondrial dysfunction could be an important determinant of cellular fate of circulating lipids, that accumulate in the cytoplasm, if they are not oxidized. The ectopic fat accumulation is associated with the development of insulin resistance, and a link between mitochondrial dysfunction and insulin resistance has been proposed

Polyunsaturated fatty acids stimulate de novo lipogenesis and improve glucose homeostasis during refeeding with high fat diet

The recovery of body weight after a period of caloric restriction is accompanied by an enhanced efficiency of fat deposition and hyperinsulinemia—which are exacerbated by isocaloric refeeding on a high fat diet rich in saturated and monounsaturated fatty acids (SFA-MUFA), and poor in polyunsaturated fatty acids (PUFA), and associated with a blunting of de novo lipogenesis in adipose tissue and liver. As high fat diets rich in PUFA have been shown to limit the excess fat deposition and improve glucose homeostasis, we investigated here the extent to which de novo lipogenesis in liver and adipose tissues (white and brown), as well as hepatic oxidative stress, are influenced by refeeding on diets rich in PUFA.Design: In rats calorically restricted for 14 days and refed for 14 days on isocaloric amounts of a high fat diet rich in lard (i.e., high SFA- MUFA) or in safflower and linseed oils (rich in PUFA), we investigated energy balance, body composition, glycemic profile, and the regulation of fatty acid synthase (rate- limiting enzyme of de novo lipogenesis) in liver, white and brown adipose tissue. We also evaluated oxidative stress in liver and skeletal muscle and markers of hepatic inflammation.Results: Rats refed the PUFA diet gained less lipids and more proteins compared to rats refed SFA-MUFA diet and showed lower amount of visceral and epididymal white adipose tissue, but increased depots of interscapular brown adipose tissue, with higher expression of the uncoupling protein 1. A significant increase in non- protein respiratory quotient and carbohydrate utilization was found in rats refed PUFA diet. Rats refed PUFA diet showed improved glucose homeostasis, as well as lower triglycerides and cholesterol levels. Fatty acid synthase activity was significantly higher in liver, white and brown adipose tissue, while lipid peroxidation and the degree of inflammation in the liver were significantly lower, in rats refed PUFA diet.Conclusions: When considering the composition of high fat diets for nutritional rehabilitation, the inclusion of PUFA could be useful for improving protein deposition and maintaining glucose homeostasis, while limiting lipid storage in adipose tissue and oxidative stress and inflammation in the liver

Exercise with Energy Restriction as a Means of Losing Body Mass while Preserving Muscle Quality and Ameliorating Co-morbidities: Towards a Therapy for Obesity?

Exercise with Energy Restriction as a Means of Losing Body Mass while Preserving Muscle Quality and Ameliorating Co-morbidities: Towards a Therapy for Obesity? Antonia Giacco1*, Elena Silvestri1*, Rosalba Senese2, Federica Cioffi1, Arianna Cuomo2, Assunta Lombardi3, Maria Moreno1, Antonia Lanni2 and Pieter de Lange()2 1Dipartimento di Science e Tecnologie, Università degli Studi del Sannio, Benevento, Italy 2Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli," Caserta, Italy 3Dipartimento di Biologia, Università degli Studi di Napoli "Federico II," Napoli, Italy © The Authors Abstract Obesity and related co-morbidities are a major public health threat worldwide, and efforts to counteract obesity by means of physiological interventions are currently being explored and applied. Here we present an overview of the literature on the effect of dietary/exercise-based programs on loss of different components of body mass. We also discuss gain or lack of loss of lean mass in view of muscle quality maintenance, which is an important aspect to consider when employing weight-loss strategies to tackle obesity. By comparing results obtained in participants with mild to severe obesity with those obtained in lean participants, we highlight variations in the success of these interventions. Furthermore, we briefly address the observation that although certain interventions may not always affect body composition they can nevertheless ameliorate co-morbidities (insulin resistance, non-alcoholic fatty liver disease). Based on what is currently known, in this narrative review we include data from human and animal studies related to the process of unravelling the mechanisms underlying conservation of functional muscle mass

Short-Term, Combined Fasting and Exercise Improves Body Composition in Healthy Males

Fasting enhances the beneficial metabolic outcomes of exercise; however, it is unknown whether body composition is favorably modified on the short term. A baseline-follow-up study was carried out to assess the effect of an established protocol involving short-term combined exercise with fasting on body composition. One hundred seven recreationally exercising males underwent a 10-day intervention across 15 fitness centers in the Netherlands involving a 3-day gradual decrease of food intake, a 3-day period with extremely low caloric intake, and a gradual 4-day increase to initial caloric intake, with daily 30-min submaximal cycling. Using dual-energy X-ray absorptiometry analysis, all subjects substantially lost total body mass (-3.9 ± 1.9 kg; p < .001) and fat mass (-3.3 ± 1.3 kg; p < .001). Average lean mass was lost (-0.6 ± 1.5 kg; p < .001), but lean mass as a percentage of total body mass was not reduced. The authors observed a loss of -3.9 ± 1.9% android fat over total fat mass (p < .001), a loss of -2.2 ± 1.9% gynoid over total fat mass (p < .001), and reduced android/gynoid ratios (-0.05 ± 0.1; p < .001). Analyzing 15 preselected single-nucleotide polymorphisms in 13 metabolism-related genes revealed trending associations for thyroid state-related single-nucleotide polymorphisms rs225014 (deiodinase 2) and rs35767 (insulin-like growth factor1), and rs1053049 (PPARD). In conclusion, a short period of combined fasting and exercise leads to a substantial loss of body and fat mass without a loss of lean mass as a percentage of total mass

Exercise with food withdrawal at thermoneutrality impacts fuel use, the microbiome, AMPK phosphorylation, muscle fibers, and thyroid hormone levels in rats

Exercise under fasting conditions induces a switch to lipid metabolism, eliciting beneficial metabolic effects. Knowledge of signaling responses underlying metabolic adjustments in such conditions may help to identify therapeutic strategies. Therefore,

Diet, Exercise, and the Metabolic Syndrome: Enrollment of the Mitochondrial Machinery

Metabolic syndrome (MS), a cluster of metabolic risk factors, ranging from abdominal obesity, dyslipidaemia, hypertension, type 2 diabetes and non-alcoholic fatty liver disease [...

Bioenergetic Aspects of Mitochondrial Actions of Thyroid Hormones

Much is known, but there is also much more to discover, about the actions that thyroid hormones (TH) exert on metabolism. Indeed, despite the fact that thyroid hormones are recognized as one of the most important regulators of metabolic rate, much remains to be clarified on which mechanisms control/regulate these actions. Given their actions on energy metabolism and that mitochondria are the main cellular site where metabolic transformations take place, these organelles have been the subject of extensive investigations. In relatively recent times, new knowledge concerning both thyroid hormones (such as the mechanisms of action, the existence of metabolically active TH derivatives) and the mechanisms of energy transduction such as (among others) dynamics, respiratory chain organization in supercomplexes and cristes organization, have opened new pathways of investigation in the field of the control of energy metabolism and of the mechanisms of action of TH at cellular level. In this review, we highlight the knowledge and approaches about the complex relationship between TH, including some of their derivatives, and the mitochondrial respiratory chain

Skeletal Muscle Mitochondrial Energetic Efficiency and Aging

Aging is associated with a progressive loss of maximal cell functionality, and mitochondria are considered a key factor in aging process, since they determine the ATP availability in the cells. Mitochondrial performance during aging in skeletal muscle is reported to be either decreased or unchanged. This heterogeneity of results could partly be due to the method used to assess mitochondrial performance. In addition, in skeletal muscle the mitochondrial population is heterogeneous, composed of subsarcolemmal and intermyofibrillar mitochondria. Therefore, the purpose of the present review is to summarize the results obtained on the functionality of the above mitochondrial populations during aging, taking into account that the mitochondrial performance depends on organelle number, organelle activity, and energetic efficiency of the mitochondrial machinery in synthesizing ATP from the oxidation of fuels