Resistance and Aerobic Training Were Effective in Activating Different Markers of the Browning Process in Obesity.

Lifestyle changes regarding diet composition and exercise training have been widely used as a non-pharmacological clinical strategy in the treatment of obesity, a complex and difficult-to-control disease. Taking the potential of exercise in the browning process and in increasing thermogenesis into account, the aim of this paper was to evaluate the effect of resistance, aerobic, and combination training on markers of browning of white adipose tissue from rats with obesity who were switched to a balanced diet with normal calorie intake. Different types of training groups promote a reduction in the adipose tissue and delta mass compared to the sedentary high-fat diet group (HS). Interestingly, irisin in adipose tissues was higher in the resistance exercise (RE) and aerobic exercise (AE) groups compared to control groups. Moreover, in adipose tissue, the fibroblast growth factor 21 (FGF21), coactivator 1 α (PGC1α), and peroxisome proliferator-activated receptor gamma (PPARγ) were higher in response to resistance training RE compared with the control groups, respectively. Additionally, uncoupling protein 1 (UCP1) showed higher levels in response to group AE compared to the HS group. In conclusion, the browning process in white adipose tissue responds differently toward different training exercise protocols, with resistance and aerobic training efficient in activating different biomarkers of the browning process, upregulating irisin, FGF21, PGC1α, PPARγ, and UCP1 in WAT, which together may suggest an improvement in the thermogenic process in the adipose tissue. Considering the experimental conditions of the present investigation, we suggest future research to pave new avenues to be applied in clinical practices to combat obesity.

Adipose tissue fibrosis in human cancer cachexia: the role of TGFß pathway.

BACKGROUND: Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFß) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFß in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGFß pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients. METHODS: After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGFß isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (αSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay. RESULTS: There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of αSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGFß1 and TGFß3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas of CC adipose tissue. CONCLUSIONS: Cancer cachexia promotes the development of AT fibrosis, in association with altered TGFß signaling, compromising AT organization and function.

A Hyperlipidic Diet Combined with Short-Term Ovariectomy Increases Adiposity and Hyperleptinemia and Decreases Cytokine Content in Mesenteric Adipose Tissue.

Four-week-old female Wistar rats were divided into two groups and fed a control diet (C) or a hyperlipidic diet (H) for 4 weeks. Rats from each group underwent ovariectomy (OVX) or sham surgery (SHAM). They received C or H for the next four weeks. The body weight gain (BW), food efficiency (FE), and carcass lipid content were higher in the OVX H than in the SHAM H. The OVX H exhibited a higher serum leptin level than other groups. IL-6, TNF-α, and IL-10 content of mesenteric (MES) adipose tissue was lower in the OVX H than in the OVX C. IL-6, TNF-α, and IL-10 content of retroperitoneal (RET) adipose tissue was lower in the SHAM H than in the SHAM C. The SHAM H showed decreased TG relative to the SHAM C. Similar results were obtained in relation to IL-6Rα, TNFR1, TLR-4, and MyD88 contents in the MES and RET white adipose tissue among the groups. A hyperlipidic diet for 8 weeks combined with short-term ovariectomy decreases the cytokine content of MES adipose tissues but increases BW, enhancing FE and elevating serum leptin levels. These suggest that the absence of estrogens promotes metabolic changes that may contribute to installation of a proinflammatory process induced by a hyperlipidic diet.

Association between ANGPTL-4 and the proinflammatory process in cancer cachexia patients.

BACKGROUND: Contradictory results are reported for the role of angiopoietin-like 4 (ANGPTL-4) in the development of cancer-cachexia and inflammation, given its importance in angiogenesis and inflammatory signaling. Our aim was to analyze the levels of ANGPTL-4 in colorectal cancer patients with a stable weight and those with cachexia in order to establish a relationship between ANGPTL-4 and the inflammatory process. RESULTS: Plasma and tumor levels of ANGPTL-4 were higher in CC in comparison to other groups. A positive association was verified between plasmatic ANGPTL-4 and NFκB levels in tumor from CC. In WSC, we identified an association between the plasmatic ANGPTL-4, IL-15, and IL-10 in tumor and IL-15 in MES. Increased levels of NFκB and TNF-R1 in MES were detected in CC in comparison to WSC. Specifically in CC-group, a positive correlation was found between ANGPTL-4 levels and those of IL-1ß, TNF-α, and NFκB in tumor, along with an association between ANGPTL-4 levels with IL-1ß and MCP-1 levels in tumor; and ANGPTL-4 and IL-1ß levels in MES. METHODS: We studied 102 patients, who were divided into three groups: control patients (C, n=37), cancer patients with a stable weight (WSC, n=23), and cancer-cachexia patients (CC, n=42). Samples of plasma, tumor, mesenteric (MES) and subcutaneous adipose tissue were removed for the determination of ANGPTL-4 levels and other proinflammatory factors. CONCLUSIONS: ANGPTL-4 levels were higher in plasma and tumor of CC-group, and positively associated with pro-inflammatory and pro-tumorigenic factors. Our results suggest an opposite effect of ANGPTL-4 depending on the concentration and presence of cachexia.

Chia flour (Salvia hispanica L.) did not improve the deleterious aspects of hyperlipidic diet ingestion on glucose metabolism, but worsened glycaemia in mice.

Obesity is mainly caused by intake of a high-fat diet and sedentarism, and is considered a public health issue worldwide. Increased intestinal permeability may favour endotoxaemia generated by lipopolysaccharides, a substance present in the cell membrane of Gram-negative bacteria, and, consequently, an increase in systemic inflammation and metabolic diseases. In contrast (On the other hand), consumption of a healthy diet can help in the prevention and treatment of metabolic syndrome. In this way, chia seeds (Salvia hispanica L.), rich in polyunsaturated fatty acids, may present an anti-inflammatory role. In addition, chia is rich in antioxidants like caffeic and gallic acid and fiber. However, few studies have investigated the relationship between chia seeds, inflammatory mechanisms and intestinal permeability. Therefore, the aim of this study was to analyse the effects of chia administration on metabolism in obese mice. Swiss mice were fed a hyperlipidic diet either supplemented with or without 3% chia flour for 16 weeks. The results showed that supplementation could not reduce the deleterious effects of the lipid-rich diet in terms of body composition, glucose intolerance and activity of antioxidants enzymes in the liver. In addition, supplementation with chia in the control diet decreased the amount of occludin in the intestinal colon. In conclusion, although chia did not improve metabolic parameters it seemed to restore the intestinal barriers integrity. The beneficial effects of chia seem to be dependent of the quantity used, since our data conflict with those in the literature; however, it is important to note that other studies, unlike our protocol, used chia in the form of seeds or oil, and not flour.

Effect of the consumption of green tea extract during pregnancy and lactation on metabolism of mothers and 28d-old offspring.

The objective was to investigate the effects of the maternal consumption of the green tea extract during pregnancy and lactation on mothers and offspring metabolism. The female Wistar rats, on the first day of pregnancy until the end of lactation, was divided into groups: MC- received water and ME- received green tea extract (400 mg/kg body weight/day), both ingested control diet. After lactation, at day 28th post-partum, the mothers and pups from each mother were euthanized and composed the groups: FC- pup from mother received water and FE- pup from mother received green tea extract. The ME group increased IL-10/TNF-α ratio and IL-1ß content in the mesenteric and IL-1ß content in retroperitoneal adipose tissues, and decreased catalase activity. The FE group decreased the retroperitoneal adipose tissue relative weight and SOD activity, but increased adiponectin, LPS, IL-10 and IL-6 content and IL-10/TNF-α ratio in retroperitoneal, IL-10 and TNF-α content in gonadal, and IL-6 content in mesenteric adipose tissues. In summary, the maternal consumption of green tea extract associated with control diet ingestion during pregnancy and lactation altered the inflammatory status of mothers and 28d-old offspring. These data elucidate the effects of green tea during pregnancy and lactation on maternal and offspring metabolism.

Peritumoural adipose tissue pro-inflammatory cytokines are associated with tumoural growth factors in cancer cachexia patients.

BACKGROUND: Cancer cachexia (CC) is a multifactorial syndrome, often irreversible, that affects patients with cancer influenced, in part, by the inflammatory condition. Peritumoural adipose tissue produces adipokines and angiogenic, apoptotic, and growth factors; given the possible crosstalk between the peritumoural adipose tissue and tumour, these may play an important role in cancer biology and carcinogenesis. METHODS: The aim of this study was to evaluate the factors produced by peritumoural adipose tissue in a cohort of 16 colorectal cancer patients with either weight-stable cancer (WSC; n = 7) or CC (n = 9). The study was approved by the Ethics Research Committee (972.914). Samples of peritumoural adipose tissue were analysed for concentrations of TNF-α, IL-1ß, STAT-1, STAT-3, RANTES, IL-1Ra, IP-10, IL-15, MCP-1, IFN-α, GCSF, FADD, and TGF-ß. The cytokines and proteins were measured using Multiplex. Correlations between the proteins and cytokines were evaluated. RESULTS: TNF-α, STAT-1, and FADD, a factor involved in apoptosis, were significantly higher in CC group than in the WSC group. In the peritumoural adipose tissue of the CC group, RANTES showed a significant positive correlation with IL-1Ra and IP-10 and a negative correlation with IFN-α; and GCSF showed significant negative correlations with IL-1Ra, IP-10, IL-15, and MCP-1 and a positive correlation with IFN-α. In the peritumoural adipose tissue of the WSC group, no significant correlations were detected between RANTES, GCSF, IL-3, FADD, and STAT-1 and the cytokines/chemokines analysed. CONCLUSIONS: These results indicated that inflammatory and tumorigenic pathways were altered in peritumoural adipose tissue in CC. Furthermore, inflammatory cytokines were correlated with growth factors in the peritumoural adipose tissue of cachectic patients, suggesting that inflammatory cytokines modulated the proliferative environment closely linked to the tumour.

Coacervate whey protein improves inflammatory milieu in mice fed with high-fat diet.

BACKGROUND: Functional foods with bioactive properties may help in treat obesity, as they can lead to a decreased risks of inflammatory diseases. The aim of this study was to investigate the effects of chitosan coacervate whey protein on the proinflammatory processes in mice fed with high-fat diet. METHODS: Mice were divided into two groups receiving either a normolipidic or high-fat diet; the animals in each of the two diet groups were given a diet supplement of either coacervate (gavage, 36 mg protein/kg of body weight) or tap water for four weeks [groups: normolipidic diet plus water (C); normolipidic diet and coacervate (CC); high-fat diet and water (H); and high-fat diet and coacervate (HC)]. RESULTS: The high-fat diet promoted inflammation, possibly by decreased adiponectin/sum of adipose tissues ratio and increased phosphorylation of NF-κB p50. In HC we observed a positive correlation between IL-10 and TNF-α in mesenteric adipose tissue, retroperitoneal adipose tissue and liver tissue. We also observed a positive correlation between lipopolisaccharide with IL-10 in the liver tissue. CONCLUSIONS: High-fat diet treatment promoted metabolic alterations and inflammation, and chitosan coacervate whey protein modulated inflammatory milieu.