Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.

Obesity is a complex disease caused by the interaction of a myriad of genetic, dietary, lifestyle and environmental factors, which favors a chronic positive energy balance, leading to increased body fat mass. There is emerging evidence of a strong association between obesity and an increased risk of cancer. However, the mechanisms linking both diseases are not fully understood. Here, we analyze the current knowledge about the potential contribution that expanding adipose tissue in obesity could make to the development of cancer via dysregulated secretion of pro-inflammatory cytokines, chemokines and adipokines such as TNF-α, IL-6, leptin, adiponectin, visfatin and PAI-1. Dietary factors play an important role in the risk of suffering obesity and cancer. The identification of bioactive dietary factors or substances that affect some of the components of energy balance to prevent/reduce weight gain as well as cancer is a promising avenue of research. This article reviews the beneficial effects of some bioactive food molecules (n-3 PUFA, CLA, resveratrol and lipoic acid) in energy metabolism and cancer, focusing on the molecular mechanisms involved, which may provide new therapeutic targets in obesity and cancer.

Several studies have suggested that oxidative stress might cause and aggravate the inflammatory state associated with obesity and could be the link between excessive weight gain and its related disorders such as insulin resistance and cardiovascular diseases. Thus, antioxidant treatment has been proposed as a therapy to prevent and manage obesity and associated complications. Therefore, the aim of the present study was to investigate the effects of supplementation of a standard or high fat diet with the antioxidant lipoic acid (LA) during 56 days, on body weight gain, adiposity, feed efficiency and intestinal sugar absorption, in male Wistar rats. LA supplementation induced a lower body weight gain and adipose tissue size in both control or high fat fed rats accompanied by a reduction in food intake. The group fed on a high fat diet and treated with LA (OLIP group) showed a lower body weight gain than its corresponding Pair-Fed (PF) group (P < 0.05), which received the same amount of food than LA-treated animals but with no LA. In fact, LA induced a reduction on feed efficiency and also significantly decreased intestinal alpha-methylglucoside (alpha-MG) absorption both in lean and obese rats. These results suggest that the beneficial effects of dietary supplementation with LA on body weight gain are mediated, at least in part, by the reduction observed in food intake and feed efficiency. Furthemore, the inhibitory action of LA on intestinal sugar transport could explain in part the lower feed efficiency observed in LA-treated animals and therefore, highlighting the beneficial effects of LA on obesity.

Irisin is a myokine/adipokine with potential role in obesity and diabetes. The objectives of the present study were to analyse the relationship between irisin and glucose metabolism at baseline and during an oral glucose tolerance test (OGTT) and to determine the effects of eicosapentaenoic acid (EPA) and/or α-lipoic acid treatment on irisin production in cultured human adipocytes and in vivo in healthy overweight/obese women following a weight loss program. Seventy-three overweight/obese women followed a 30% energy-restricted diet supplemented without (control) or with EPA (1.3 g/day), α-lipoic acid (0.3 g/day) or both EPA + α-lipoic acid (1.3 + 0.3 g/day) during 10 weeks. An OGTT was performed at baseline. Moreover, human adipocytes were treated with EPA (100-200 μM) or α-lipoic acid (100-250 μM) during 24 h. At baseline plasma, irisin circulating levels were positively associated with glucose levels; however, serum irisin concentrations were not affected by the increment in blood glucose or insulin during the OGTT. Treatment with α-lipoic acid (250 μM) upregulated Fndc5 messenger RNA (mRNA) and irisin secretion in cultured adipocytes. In overweight/obese women, irisin circulating levels decreased significantly after weight loss in all groups, while no additional differences were induced by EPA or α-lipoic acid supplementation. Moreover, plasma irisin levels were positively associated with higher glucose concentrations at beginning and at endpoint of the study. The data from the OGTT suggest that glucose is not a direct contributing factor of irisin release. The higher irisin levels observed in overweight/obese conditions could be a protective response of organism to early glucose impairments.

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This article is available online at http://www.jlr.org properties. In fact, LA is able to directly scavenge reactive oxygen species (ROS) and regenerate endogenous antioxidants, such as glutathione and vitamins E and C ( 1, 2 ). Moreover, several studies have described potential beneficial effects of LA on obesity and its associated comorbidities, such as insulin resistance, type 2 diabetes, or fatty liver diseases. Thus, in rodents LA has been shown to cause profound weight loss by reducing food intake and enhancing energy expenditure ( 3 ) as well as by inducing a reduction on intestinal sugar absorption ( 4 ). More recently, two clinical trials in humans reported that LA caused signifi cant reductions of body weight, body mass index, blood pressure, and abdominal circumference in obese subjects ( 5, 6 ). LA also improved insulin sensitivity and plasma lipid profi le possibly through amelioration of oxidative stress and chronic infl ammatory status in obese patients with impaired glucose tolerance ( 7 ). Previous studies have provided strong evidence that LA is able to deeply affect adipose tissue development and function by the inhibition of adipogenesis ( 8 ), the regulation of the secretion of several adipokines such as leptin ( 9 ) and apelin ( 10 ), and by the promotion of mitochondrial biogenesis ( 11 ).In this context, previous studies suggested that LA seems to stimulate the lipolytic response in an in vitro model of broiler chicken adipocytes ( 12 ). However, the molecular mechanisms that mediate these effects remain unclear. Lipolysis is a complex process that is highly regulated and Lipoic acid (LA), or 1,2-dithiolane-3-pentaenoic acid, is a naturally occurring compound that contains two thiol groups with diverse benefi cial effects on health. The biological effects of LA were primarily associated with its antioxidant This work was supported, in part,

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Lipodystrophy encompass a group of heterogeneous disorders consisting in marked reduction, absence, and/or the redistribution of adipose tissue. Lipodystrophy is frequently complicated with severe insulin resistance, diabetes, hyperlipidemia, and fatty liver. Anatomically, lipodystrophies can be partial or generalized. Etiologically, they can be congenital or acquired. Lipodystrophy diagnosis can be challenging, and it has been suggested that partial forms can be easily misdiagnosed as common central obesity with associated metabolic syndrome. Conventional insulin-sensitizing approaches usually fail to fully ameliorate insulin resistance in lipodystrophic patients. Leptin replacement is an approved therapy for the metabolic complications of congenital generalized lipodystrophy. Novel nutritional interventions are promising complementary approaches for treating lipodystrophy metabolic complications.