Maternal obesity may compromise the micronutrient status of the offspring. Vitamin A (VA) is an essential micronutrient during neonatal development. Its active metabolite, retinoic acid (RA), is a key regulator of VA homeostasis, which also regulates adipose tissue (AT) development in obese adults. However, its role on VA status and AT metabolism in neonates was unknown and it was determined in the present study. Pregnant Sprague-Dawley rats were randomised to a normal fat diet (NFD) or a high fat diet (HFD). From postnatal day 5 (P5) to P20, half of the HFD pups received oral RA every 3 d (HFDRA group). NFD pups and the remaining HFD pups (HFD group) received placebo. Six hours after dosing on P8, P14 and P20, n 4 pups per group were euthanised for different measures. It was found that total retinol concentration in neonatal liver and lung was significantly lower in the HFD group than the NFD group, while the concentrations were significantly increased in the HFDRA group. The HFD group exhibited significantly higher body weight (BW) gain, AT mass, serum leptin and adiponectin, and gene expression of these adipokines in white adipose tissue compared with the NFD group; these measures were significantly reduced in the HFDRA group. BAT UCP2 and UCP3 gene expression were significantly higher in pups receiving RA. In conclusion, repeated RA treatment during the suckling period improved the tissue VA status of neonates exposed to maternal obesity. RA also exerted a regulatory effect on neonatal obesity development by reducing BW gain and adiposity and modulating AT metabolism.

The present study aimed to investigate an interaction between energy intake, physical activity and UCP2 gene variation on weight gain and adiposity changes in Indonesian adults. This is a prospective cohort study conducted in 323 healthy adults living in the city of Yogyakarta, Indonesia. Energy intake, physical activity, body weight, BMI, percentage body fat and waist:hip ratio (WHR) were measured at baseline and after 2 years while UCP2 -866G/A gene variation was determined at baseline. We reported that after 2 years subjects had a significant increment in body weight, BMI, body fat and reduction in WHR (all P < 0·05). In all subjects, total energy intake was significantly correlated with changes in body weight (β = 0·128, P = 0·023) and body fat (β = 0·123, P = 0·030). Among subjects with the GG genotype, changes in energy intake were positively correlated with changes in body weight (β = 0·232, P = 0·016) and body fat (β = 0·201, P = 0·034). These correlations were insignificant among those with AA + GA genotypes (all P > 0·05). In summary, we show that UCP2 gene variation might influence the adiposity response towards changes in energy intake. Subjects with the GG genotype of UCP2 -866G/A gene were more responsive to energy intake, thus more prone to weight gain due to overeating.

Mitochondria play an important role in a number of fundamental cellular processes, including energy production, biosynthetic pathways and cellular oxidoreductive homeostasis (redox status), and their dysfunction can lead to numerous pathophysiological consequences. As the biochemical mechanisms orchestrating mitochondrial metabolism and redox homeostasis are functionally linked, mitochondria have been identified as a potential therapeutic target. Consequently, considerable effort has been made to evaluate the efficacy of natural compounds that modulate mitochondrial function. Molecules produced by plants (for example, polyphenols and isothiocyanates) have been shown to modulate mitochondrial metabolism/biogenesis and redox status; however, despite the existence of a functional link, few studies have considered the combined efficacy of these mitochondrial functions. The present review provides a complete overview of the molecular pathways involved in modulating mitochondrial metabolism/biogenesis and redox status. Crosstalk between these critical mechanisms is also discussed, whilst major data from the literature regarding their antioxidant abilities are described and critically analysed. We also provide a summary of recent evidence regarding the ability of several plant-derived compounds to target these mitochondrial functions. An in-depth understanding of the functional link between mitochondrial metabolism/biogenesis and redox status could facilitate the analysis of the biological effects of natural compounds as well as the development of new therapeutic approaches.

Cancer-associated malnutrition is driven by reduced dietary intake and by underlying metabolic changes (such as inflammation, anabolic resistance, proteolysis, lipolysis and futile cycling) induced by the tumour and activated immune cells. Cytotoxic and targeted chemotherapies also elicit proteolysis and lipolysis at the tissue level. In this review, we summarise specific mediators and chemotherapy effects that provoke excess proteolysis in muscle and excess lipolysis in adipose tissue. A nutritionally relevant question is whether and to what degree these catabolic changes can be reversed by nutritional therapy. In skeletal muscle, tumour factors and chemotherapy drugs activate intracellular signals that result in the suppression of protein synthesis and activation of a transcriptional programme leading to autophagy and degradation of myofibrillar proteins. Cancer nutrition therapy is intended to ensure adequate provision of energy fuels and a complete repertoire of biosynthetic building blocks. There is some promising evidence that cancer- and chemotherapy-associated metabolic alterations may also be corrected by certain individual nutrients. The amino acids leucine and arginine provided in the diet at least partially reverse anabolic suppression in muscle, while n-3 PUFA inhibit the transcriptional activation of muscle catabolism. Optimal conditions for exploiting these anabolic and anti-catabolic effects are currently under study, with the overall aim of net improvements in muscle mass, functionality, performance status and treatment tolerance.

Obesity is one of the major health problems throughout the world. The present study investigated the preventive effect of epilactose – a rare non-digestible disaccharide – on obesity and metabolic disorders in mice fed high-fat (HF) diets. Feeding with HF diets increased body weight gain, fat pad weight and adipocyte size in mice (P<0·01), and these increases were effectively prevented by the use of supplemental epilactose without influencing food intake (P<0·01). Caecal pools of SCFA such as acetic and propionic acids in mice fed epilactose were higher compared with mice not receiving epilactose. Supplemental epilactose increased the expression of uncoupling protein (UCP)-1, which enhances energy expenditure, to 2-fold in the gastrocnemius muscle (P=0·04) and to 1·3-fold in the brown adipose tissue (P=0·02) in mice fed HF diets. Feeding HF diets induced pro-inflammatory macrophage infiltration into white adipose tissue, as indicated by the increased expression of monocyte chemotactic protein-1, TNF-α and F4/80, and these increases were attenuated by supplemental epilactose. In differentiated myogenic-like C2C12 cells, propionic acid, but not acetic or n-butyric acids, directly enhanced UCP-1 expression by approximately 2-fold (P<0·01). Taken together, these findings indicate that the epilactose-mediated increase in UCP-1 in the skeletal muscle and brown adipose tissue can enhance whole-body energy expenditure, leading to effective prevention of obesity and metabolic disorders in mice fed HF diets. It is suggested that propionic acid – a bacterial metabolite – acts as a mediator to induce UCP-1 expression in skeletal muscles.

Energy restriction (ER; also known as caloric restriction) is the only nutritional intervention that has repeatedly been shown to increase lifespan in model organisms and may delay ageing in humans. In the present review we discuss current scientific literature on ER and its molecular, metabolic and hormonal effects. Moreover, criteria for the classification of substances that might induce positive ER-like changes without having to reduce energy intake are summarised. Additionally, the putative ER mimetics (ERM) 2-deoxy-d-glucose, metformin, rapamycin, resveratrol, spermidine and lipoic acid and their suggested molecular targets are discussed. While there are reports on these ERM candidates that describe lifespan extension in model organisms, data on longevity-inducing effects in higher organisms such as mice remain controversial or are missing. Furthermore, some of these candidates produce detrimental side effects such as immunosuppression or lactic acidosis, or have not been tested for safety in long-term studies. Up to now, there are no known ERM that could be recommended without limitations for use in humans.

We previously described that the intake of pharmacological doses of β-carotene (BC) resulted in higher body weight gain in the ferret (Mustela putorius furo), an animal model that resembles human subjects in terms of intestinal BC absorption and metabolism. These results were some way unexpected considering the condition of BC as a vitamin A precursor and the previous data in rodents showing these compounds as thermogenic activators. Here, we aimed to characterise in the ferret whether the mentioned changes in body weight could be explained by changes in adipose tissue thermogenic capacity. We studied the effects of 6-month supplementation with BC (0·8 and 3·2 mg/kg per d) on adipose tissue morphology and uncoupling protein-1 (UCP1) content. BC supplementation resulted in higher body weight (the high dose), induced depot- and dose-dependent hypertrophy of white adipocytes, decreased the amount of brown-like multilocular adipocytes in the retroperitoneal depot and decreased UCP1 content in different fat depots. To ascertain whether BC effects could be mediated by retinoic acid (RA), 1 week supplementation with RA (0·25 and 25 mg/kg per d) was also studied. RA treatment resulted in a slight decrease in adiposity, decreased cell lipid accumulation and increased UCP1 content, suggesting that the effects of BC on thermogenic capacity are not through RA. In conclusion, RA, but not BC, may have in the ferret comparable effects with those described in rodents, whereas differences concerning BC and RA treatments may be attributable to the different BC metabolism in the present animal model with a lower conversion of BC to RA compared with rodents.

Few researchers would dispute that the pandemic of obesity is caused by a profound mismatch between humanity's present environmental circumstances and those that have moulded evolutionary selection. This concept was first articulated when gestational diabetes was described as being the result of a ‘thrifty genotype rendered detrimental by progress’. More recently, this hypothesis has been extended to the concept of a ‘thrifty phenotype’ to describe the metabolic adaptations adopted as a survival strategy by a malnourished fetus; changes that may also be inappropriate to deal with a later life of affluence. Both the thrifty genotype and the thrifty phenotype hypotheses would predict that populations in some areas of the developing world would be at greater risk of obesity and its co-morbidities; a proposition to be explored in the present paper. To date thrifty genes remain little more than a nebulous concept propagated by the intuitive logic that man has been selected to survive episodic famine and seasonal hungry periods. Under such conditions those individuals who could lay down extra energy stores and use them most efficiently would have a survival advantage. The search for candidate thrifty genes needs to cover every aspect of human energy balance from food-seeking behaviour to the coupling efficiency of oxidative phosphorylation. The present paper will describe examples of attempts to find thrifty genes in three selected candidate areas: maternally-transmitted mitochondrial genes; the uncoupling proteins; apoE4, whose geographical distribution has been linked to a possible thrifty role in lipoprotein and cholesterol metabolism.

Leptin is a 16 kDa hormone which has been shown to have a major physiological role in the control of energy balance. Leptin is produced primarily in white adipose tissue, although there is evidence for its production in brown adipose tissue (BAT) and the placenta. BAT is critically important for the initiation of non-shivering thermogenesis in the newborn through the BAT-specific uncoupling protein (UCP), UCP1. This factor is particularly important in lambs in which levels of UCP1 peak at birth, concomitant with a rapid decline in plasma leptin levels. Our studies have examined the effect of acute and chronic administration of leptin to neonatal lambs, investigating effects on colonic temperature, UCP1 and thermogenic potential of BAT. Administration of leptin in sequential physiological doses of 10, 100 and 100 µg to neonatal lambs caused a modest increase in colonic temperature which was not observed in weight-matched vehicle-treated controls. This increase in colonic temperature was not mediated by an increase in either abundance or thermogenic potential of UCP1, as previously shown in adult rodents. UCP1 mRNA levels were 30 % lower in leptin-treated lambs, which is also contradictory to findings in adult rodents. Leptin treatment resulted in a dose-dependent rise in plasma leptin, with levels at the end of the study being almost twenty times greater in leptin-treated animals. To determine whether these findings in neonatal lambs were transient due to the complex milieu of hormones present after birth, we examined the effect of chronic leptin treatment over 6 d. Pairs of lambs were treated daily, from the second to seventh day of life with 100 µg leptin or vehicle. Colonic temperatures of leptin- and vehicle-treated animals remained similar throughout the study. UCP1 abundance was significantly lower in the leptin-treated animals, suggesting that the drop in UCP1 mRNA seen in the previous study had been translated to protein levels. In conclusion, the decline in plasma leptin levels at birth may be a signal to initiate enteral feeding. In lambs, the rapid loss of UCP1 mRNA, which occurs within the first few days of life, appears to be accelerated by leptin administration, possibly stimulating the development of white adipose tissue and generation of body heat through mechanisms other than non-shivering thermogenesis by UCP1 in BAT.