Accumulating evidence indicates that dietary phenolic compounds can prevent obesity-related disorders. We investigated whether the consumption of polyphenol-rich jabuticaba peel and seed powder (JPSP) could ameliorate the progression of diet-induced obesity in mice. Male mice were fed a control diet or a high-fat (HF) diet for 9 weeks. After this period, mice were fed control, HF or HF diets supplemented with 5 % (HF-J5), 10 % (HF-J10) or 15 % (HF-J15) of JPSP, for 4 additional weeks. Supplementation with JPSP not only attenuated HF-induced weight gain and fat accumulation but also ameliorated the pro-inflammatory response associated with obesity, as evidenced by the absence of mast cells in the visceral depot accompanied by lower IL-6 and TNF-α at the tissue and circulating levels. JPSP-supplemented mice also exhibited smaller-sized adipocytes, reduced levels of leptin and higher levels of adiponectin, concomitant with improved glucose metabolism and insulin sensitivity. The magnitude of the observed effects was dependent on JPSP concentration with HF-J10- and HF-J15-fed mice showing metabolic profiles similar to control. This study reveals that the consumption of JPSP protects against the dysfunction of the adipose tissue and metabolic disturbances in obese mice. Thus, these findings indicate the therapeutic potential of the phenolic-rich JPSP in preventing obesity-related disorders.

Menopausal women are susceptible to osteoarthritis(OA) and memory impairment. We hypothesised that Alzheimer’s-like disease(AD) exacerbates OA and that intermittent fasting(IMF) with a high-protein(H-P) diet would enhance memory function and relieve OA symptoms in oestrogen-deficient animals induced AD and OA. The action mechanism was also explored. Ovariectomised Sprague–Dawley rats were fed high-fat(H-F) or H-P diets for 2 weeks, and then they had a hippocampal infusion of β-amyloid(25–35) for 4 weeks to induce AD and an injection of monoidoacetate(MIA) into the articular cartilage to induce OA. Non-AD groups had non-AD symptoms by hippocampal amyloid-β(35–25) infusion. IMF suppressed memory impairment in AD rats, especially those fed H-P diets. Compared with non-AD, AD exacerbated OA symptoms, including swelling, limping, slowed treadmill running speed, and uneven weight distribution in the left leg. The exacerbations were linked to increased inflammation and pain, but IMF and H-P lessened the exacerbation. Lean body mass(LBM) decreased with AD, but H-P protected against LBM loss. Histological examination of the knee joint revealed the degree of the cellular invasion into the middle zone, and the changes in the tidemark plateau were greatest in the AD-AL with H-F, while non-AD-IMF improved the cellular invasion to as much as non-AD-AL. H-P reduced the infiltration into the middle zone of the knee and promoted collagen production. In conclusion, AD exacerbated the articular cartilage deterioration and memory impairment, and IMF with H-P alleviated the memory impairment and osteoarthritic symptoms by decreasing hippocampal amyloid-β deposition and proinflammatory cytokine expressions and by increasing LBM.

The aim of this study was to examine the effect of three different fatty acid (FA)-rich meals enriched in either SFA, MUFA or PUFA on postprandial metabolic responses in premenopausal, normal-weight women. For this randomised, single-blind, crossover study, three high-fat (HF) meals rich in either SFA, MUFA or PUFA (65 % energy from fat; 35 % of participants’ total daily energy needs) were tested. For each visit, anthropometrics and RMR were measured following a 12–15 h fast. Then, participants consumed one of the HF meals, and respiratory gases were collected using indirect calorimetry for 3 h postprandially. Energy expenditure (EE) following a SFA-rich meal was significantly higher than a MUFA-rich meal (P = 0·04; η2 = 0·19), but SFA was not significantly different from PUFA. There was a trend towards significance in EE between PUFA and MUFA (P = 0·06). After adjusting for fat-free mass (FFM), there were no longer condition or time effects for EE, although FFM remained a significant predictor (P = 0·005; η2 = 0·45). There were no significant differences between conditions for dietary-induced thermogenesis or substrate oxidation. The relationship between fat mass (FM) and both total fat oxidation (r 0·62; P = 0·025) and total change in RER following a MUFA-rich meal was observed (r −0·55; P = 0·05). In conclusion, weight loss through increases in EE may be best achieved by increasing FFM rather than selection of FA type. Further, a relationship exists between FM and fat oxidation following a MUFA-rich meal, most likely due to an unidentified mechanism.

Hyperlipidaemia and cognitive dysfunction (CD) are the two public health concerns. Though hyperlipidaemia has been comprehensively studied in respect to CVD, its role on CD needs to be explored. Hence, we evaluated hyperlipidaemia as a risk factor for CD and the efficacy of EPA (20 : 5n-3) + DHA (22 : 6n-3) and zerumbone (Z) in modulating CD under hyperlipidaemic conditions. Male Wistar rats (Rattus norvegicus) were fed control, high-fat (HF), high-fat + fish oil (HF + F), high-fat + zerumbone (HF+Z) and high-fat + fish oil + zerumbone (HF+F+Z) containing diets. After a 30 d feeding trial, memory parameters (Morris water maze, elevated plus maze (transfer latency) and T-maze (spontaneous alteration)) and locomotor skills (open field test and rotarod test) were assessed. Hyperlipidaemia significantly (P < 0·05) reduced memory and motor coordination skills compared with control. However, the administration of EPA + DHA and zerumbone significantly (P < 0·05) restored the hyperlipidaemia-induced loss of memory and motor coordination skills. Collectively, our data imply that hyperlipidaemia causes CD by decreasing memory and motor coordination skills, and administration of EPA + DHA and zerumbone prevents hyperlipidaemia-induced CD. The augmented effect of EPA + DHA, together with zerumbone, discloses a promising strategy for lowering the severity of CD in hyperlipidaemic conditions.

The gut microbiota is directly influenced by dietary components, and it plays critical roles in chronic diseases. Excessive consumption of trans-fatty acids (TFA) is associated with obesity induced by alterations in gut microbiota, but the links between obesity and gut microbiota remain unclear. Therefore, studies examining the impact of TFA on intestinal microflora are essential. In our study, we performed 16S ribosomal RNA gene sequencing on faecal samples from Sprague–Dawley rats fed a basal diet (control (CON) group), high-fat (HF) diet (diet-induced obesity (DIO) group) or TFA diets (1 % TFA group and 8 % TFA group) for 8 weeks to investigate the effects of TFA/HF diets on obesity and gut microbiota composition. We found that the TFA/HF diets significantly induced obesity and changes in blood and brain physiological parameters of the rats. The relative abundance of the phyla Firmicutes and Bacteroidetes was inversely altered in the three test groups compared with the CON group. Proteobacteria increased slightly in the DIO, 1 % TFA and 8 % TFA groups. The genus Bacteroides increased in the DIO and 1 % TFA groups, but Muribaculaceae decreased in all experimental groups compared with the CON group. Moreover, significant differences were observed among clusters of orthologous group functional categories of the four dietary groups. Our observations suggested that the TFA/HF diets induced obesity and dysfunction of gut microbiota. Gut dysbiosis might mediate the obesity effects of TFA/HF diets.

Treatment of liver fibrosis is very limited as there is currently no effective anti-fibrotic therapy. Spirulina platensis (SP) is a blue-green alga that is widely supplemented in healthy foods. The objective of this study was to determine whether SP supplementation can prevent obesity-induced liver fibrosis in vivo. Male C57BL/6J mice were randomly assigned to a low-fat or a high-fat (HF)/high-sucrose/high-cholesterol diet or an HF diet supplemented with 2·5 % SP (w/w) (HF/SP) for 16 or 20 weeks. There were no significant differences in body weight, activity, energy expenditure, serum lipids or glucose tolerance between mice on HF and HF/SP diets. However, plasma alanine aminotransferase level was significantly reduced by SP at 16 weeks. Expression of fibrotic markers and trichrome stains showed no differences between HF and HF/SP. Splenocytes isolated from HF/SP fed mice had lower inflammatory gene expression and cytokine secretion compared with splenocytes from HF-fed mice. SP supplementation did not attenuate HF-induced liver fibrosis. However, the expression and secretion of inflammatory genes in splenocytes were significantly reduced by SP supplementation, demonstrating the anti-inflammatory effects of SP in vivo. Although SP did not show appreciable effect on the prevention of liver fibrosis in this mouse model, it may be beneficial for other inflammatory conditions.

We have recently reported that soluble dietary fibre, glucomannan, increased colonic alkaline phosphatase (ALP) activity and the gene expression without affecting the small-intestinal activity and that colonic ALP was correlated with gut mucins (index of intestinal barrier function). We speculated that dietary fermentable carbohydrates including oligosaccharides commonly elevate colonic ALP and gene expression as well as increase mucin secretion and microbial fermentation. To test this hypothesis, male Sprague–Dawley rats were fed a diet containing 30 % lard with or without 4 % fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), raffinose (RAF) and lactulose (LAC), which are non-digestible oligosaccharides or isomalto-oligosaccharides (IMOS; some digestible oligosaccharides) for 2 weeks. Colon ALP activity, the gene expression and gut luminal variables including mucins, organic acids and microbiota were measured. Colonic ALP was significantly elevated in the FOS, RAF and LAC groups, and a similar trend was observed in the GOS group. Colonic expression of intestinal alkaline phosphatase (IAP-I), an ALP gene, was significantly elevated in the FOS, GOS and RAF groups and tended to be increased in the LAC group. Dietary FOS, GOS, RAF and LAC significantly elevated faecal mucins, caecal n-butyrate and faecal ratio of Bifidobacterium spp. Dietary IMOS had no effect on colonic ALP, mucins, organic acids and microbiota. Colon ALP was correlated with mucins, caecal n-butyrate and faecal Bifidobacterium spp. This study demonstrated that non-digestible and fermentable oligosaccharides commonly elevate colonic ALP activity and the expression of IAP-I, with increasing mucins and microbial fermentation, which might be important for protection of gut epithelial homoeostasis.

This study evaluated the effects of a post-weaning high-fat (HF) diet on somatic growth, food consumption, metabolic parameters, phagocytic rate and nitric oxide (NO) production of peritoneal macrophages in young rats submitted to a maternal low-protein (LP) diet. Male Wistar rats (aged 60 d) were divided in two groups (n 22/each) according to their maternal diet during gestation and lactation: control (C, dams fed 17 % casein) and LP (dams fed 8 % casein). At weaning, half of the groups were fed HF diet and two more groups were formed (HF and low protein–high fat (LP-HF)). Somatic growth, food and energy intake, fat depots, serum glucose, cholesterol and leptin concentrations were evaluated. Phagocytic rate and NO production were analysed in peritoneal macrophages under stimulation of zymosan and lipopolysaccharide (LPS)+interferon γ (IFN-γ), respectively. The maternal LP diet altered the somatic parameters of growth and development of pups. LP and LP-HF pups showed a higher body weight gain and food intake than C pups. HF and LP-HF pups showed increased retroperitoneal and epididymal fat depots, serum level of TAG and total cholesterol compared with C and LP pups. After LPS+IFN-γ stimulation, LP and LP-HF pups showed reduced NO production when compared with their pairs. Increased phagocytic activity and NO production were seen in LP but not LP-HF peritoneal macrophages. However, peritoneal macrophages of LP pups were hyporesponsive to LPS+IFN-γ induced NO release, even after a post-weaning HF diet. Our data demonstrated that there was an immunomodulation related to dietary fatty acids after the maternal LP diet-induced metabolic programming.

As obesity and metabolic diseases rise, there is need to investigate physiological and behavioural aspects associated with their development. Circadian rhythms have a profound influence on metabolic processes, as they prepare the body to optimise energy use and storage. Moreover, food-related signals confer temporal order to organs involved in metabolic regulation. Therefore food intake should be synchronised with the suprachiasmatic nucleus (SCN) to elaborate efficient responses to environmental challenges. Human studies suggest that a loss of synchrony between mealtime and the SCN promotes obesity and metabolic disturbances. Animal research using different paradigms has been performed to characterise the effects of timing of food intake on metabolic profiles. Therefore the purpose of the present review is to critically examine the evidence of animal studies, to provide a state of the art on metabolic findings and to assess whether the paradigms used in rodent models give the evidence to support a ‘best time’ for food intake. First we analyse and compare the current findings of studies where mealtime has been shifted out of phase from the light–dark cycle. Then, we analyse studies restricting meal times to different moments within the active period. So far animal studies correlate well with human studies, demonstrating that restricting food intake to the active phase limits metabolic disturbances produced by high-energy diets and that eating during the inactive/sleep phase leads to a worse metabolic outcome. Based on the latter we discuss the missing elements and possible mechanisms leading to the metabolic consequences, as these are still lacking.

Peripheral blood mononuclear cells (PBMC) are increasingly used for nutrigenomic studies. In this study, we aimed to identify whether these cells could reflect the development of an obesogenic profile associated with the intake of high-fat (HF) diets. We analysed, by real-time RT-PCR, the dietary response of key genes related to lipid metabolism, obesity and inflammation in PBMC of control rats, rats fed a cafeteria or a commercial HF diet and rats fed a control diet after the intake of a cafeteria diet (post-cafeteria model). Cafeteria diet intake, which resulted in important overweight and related complications, altered the expressions of most of the studied genes in PBMC, evidencing the development of an obesogenic profile. Commercial HF diet, which produced metabolic alterations but in the absence of noticeably increased body weight, also altered PBMC gene expression, inducing a similar regulatory pattern as that observed for the cafeteria diet. Regulation of carnitine palmitoyltransferase I (Cpt1a) mRNA expression was of special interest; its expression reflected metabolic alterations related to the intake of both obesogenic diets (independently of increased body weight) even at an early stage as well as metabolic recovery in post-cafeteria animals. Thus, PBMC constitute an important source of biomarkers that reflect the increased adiposity and metabolic deregulation associated with the intake of HF diets. In particular, we propose an analysis of Cpt1a expression as a good biomarker to detect the early metabolic alterations caused by the consumption of hyperlipidic diets, and also as a marker of metabolic recovery associated to weight loss.

Hypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia.

The present study aimed to compare the action of high-fat and high-carbohydrate (CHO) foods on meal size (satiation) and post-meal satiety in obese women. A within-subjects design was used; each participant received all four nutritional challenges. Fifteen healthy obese women (age 21–56 years, BMI 35–48 kg/m2) participated; thirteen completed all four test days. On two test days, participants were exposed to a nutritional challenge comprising an ad libitum high-fat or high-CHO lunch. On the other two test days they were exposed to a challenge comprising an ad libitum sweet high-fat or high-CHO mid-afternoon snack. Energy and macronutrient intakes were measured at each eating episode. Visual analogue rating scales were completed periodically to record subjective feelings of appetite. When offered a high-CHO selection of foods at lunch and mid-afternoon participants consumed less energy than when offered a high-fat selection. However, post-meal satiety was similar. Total test-day energy intake was significantly higher when high-fat foods were consumed at lunch, but not as a snack. Consumption of high-fat foods at a lunch and snack increased the amount of fat consumed over the whole test day. In conclusion, energy intake of an eating episode was influenced by nutrient composition in this group of obese women. Consumption of high-fat foods at lunch or as a snack led to overconsumption relative to high-CHO foods. However, high-fat foods at meals may have greater potential to influence daily intake than at snacks, probably because meals are larger eating episodes and therefore give greater opportunity to overconsume.

Gain in body weight over a number of years could be achieved through cumulative positive energy balances. These positive balances could come about through adjustments in the various components of energy expenditure or fuel utilization, together with shifts in food selection or eating patterns leading to adjustments in macronutrient intake. This means that many combinations of intake and expenditure could lead to a positive energy balance; these combinations can be called routes to body weight gain. However, these routes are difficult to trace by studying random samples of individuals. Previous investigations have found a clear association between high fat consumption and the occurrence of obesity, and although a high fat intake is a strong behavioural risk factor for weight gain, the relationship does not constitute a biological inevitability. Some normal-weight and lean individuals appear to eat a high-fat diet. To investigate reasons for this we have studied individuals initially defined by particular clusters of dietary characteristics related to fat and carbohydrate consumption. Habitual high-fat (HF) and low-fat (LF) consumers have been termed phenotypes. Various aspects of energy expenditure (physiological and behavioural) and energy intake were measured in these individuals with contrasting profiles. HF phenotypes had high intakes of fatty foods and an overall higher energy intake than LF. However, these groups of young adult males had similar BMIs and percentage body fat. The HF had a significantly higher resting metabolic rate (RMR) and a lower RQ, together with high plasma fasting leptin levels, and a higher sleeping heart rate. In HF individuals the physical activity level was somewhat lower and they had significantly more periods of sedentary behaviour than LF subjects. Although HF individuals appear to be more vulnerable to developing obesity, both phenotypes carry particular risk factors and protective factors for weight gain. The use of phenotypes has allowed the identification of different potential routes to weight gain. Different strategies are required to prevent age-related increase in body weight in these quite different individuals.