Relationship Between Zinc, Selenium, and Magnesium Status and Markers of Metabolically Healthy and Unhealthy Obesity Phenotypes.

Our objective was to investigate the relationship between zinc, selenium, and magnesium status and markers of metabolically healthy and unhealthy obesity phenotypes. This was a cross-sectional study with 140 women: metabolically healthy obese women (n = 35), metabolically unhealthy obese women (n = 28), and normal-weight women (n = 77). We have calculated the body mass index, waist-hip ratio, waist-height ratio and some adiposity indices. Additionally, we evaluated endocrine-metabolic parameters and estimated the dietary intake of energy, macronutrients, zinc, selenium, and magnesium. The mineral concentrations in plasma, erythrocytes, and urine were assessed. In obese patients, there was a significant decrease in dietary zinc, selenium, and magnesium intake per kilogram of body weight, as well as lower mineral concentrations in both plasma and erythrocytes. Additionally, these patients exhibited higher urinary mineral levels compared to the control group, regardless of whether they had healthy or unhealthy phenotypes. We observed a significant correlation between deficiencies in zinc, selenium, and magnesium and obesity-associated metabolic disorders, including dyslipidemias and redox status disturbances. This study highlights a connection between deficiencies in zinc, selenium, and magnesium and metabolic disorders linked to obesity, including dyslipidemias, alterations in redox status, and thyroid hormonal dysfunction.

No association between zinc and thyroid activity in obese women.

Obesity is characterized by changes in the metabolism of zinc and thyroid hormones. Studies have also shown the role of zinc in the function and metabolism of thyroid. The present study aimed to evaluate the relationship between serum concentrations of thyroid hormones, dietary zinc intake and zinc distribution in obese women. A case-control study was conducted enrolling 98 women aged between 20 and 50 years old who were divided into case group (BMI ≥ 35 kg/m2) and control group (BMI = 18.5-24.9 kg/m2). Patients underwent anthropometric measurements and analysis of dietary zinc intake, which was performed by a three-day food record. Zinc concentrations in plasma and erythrocytes were determined by inductively coupled plasma optical emission spectrometry. Serum concentrations of thyroid hormones and antibodies were determined by chemiluminescence. Mean values of dietary zinc intake were higher than recommended (10.37 ± 3.12 mg/day and 11.37 ± 4.36 mg/day for control and obeses, respectively). Obese women had reduced plasma (67.22 ± 5.96 µg/dL) and erythrocyte (37.16 ± 3.64 µg Zn/gHb) zinc concentrations when compared to the control group (plasma: 89.71 ± 13.33 µg/dL; erythrocyte: 42.68 ± 3.73 µg Zn/gHb) (p < 0.001). Serum TSH (control: 2.62 ± 1.29 µIU/mL; obeses: 3.08 ± 1.13 µIU/mL), Free T3 (control: 2.19 ± 0.63 pg/dL; obeses: 2.09 ± 0.34 pg/dL), and Free T4 (control: 1.12 ± 0.31 ng/dL; obeses: 1.09 ± 0.19 ng/dL) concentrations were within the normal range in both groups, without significant difference between them (p > 0.05). There was no correlation between thyroid hormone concentrations and zinc parameters (p > 0.05). Although obese women presented hypozincemia, they had normal levels of thyroid hormones and no correlation was found between the studied parameters.

Win 55,212-2, atenolol and subdiaphragmatic vagotomy prevent acceleration of gastric emptying induced by cachexia via Yoshida-AH-130 cells in rats.

The aim of this study was to investigate the effect of cachexia induced by AH-130 cells on gastrointestinal motility in rats. We evaluated food intake, body weight variation, cachexia index, gastric emptying and in vitro gastric responsiveness of control or cachexia rats. In addition, we evaluated the effect of pretreatment with atenolol (20 mg/kg, p.o.), win 55,212-2 (2 mg/kg, s.c.) or subdiaphragmatic vagotomy on the effects found. Atenolol prevented (P < 0.05) the acceleration of gastric emptying (area under the curve, AUC, 20360.17 ± 1970.9 vs. 12579.2 ± 785.4 µg/min/ml), and increased gastric responsiveness to carbachol (CCh) stimulation in cachectic rats compared to control groups (CCh-6M: 63.2 ± 5.5% vs. 46.5 ± 5.7%). Vagotomy prevented (P < 0.05) increase in gastric emptying acceleration (AUC 20360.17 ± 1970.9 vs. 13414.0 ± 1112.9 µg/min/ml) and caused greater in vitro gastric responsiveness of cachectic compared to control rats (CCh-6M: 63.2 ± 5.5% vs. 31.2 ± 4.7%). Win 55,212-2 attenuated the cachexia index (38.5 ± 2.1% vs. 25.8 ± 2.7%), as well as significantly (P < 0.05) preventing increase in gastric emptying (AUC 20360.17 ± 1970.9 vs. 10965.4 ± 1392.3 µg/min/ml) and gastric responsiveness compared to control groups (CCh-6M: 63.2 ± 5.5% vs. 38.2 ± 3.9%). Cachexia accelerated gastric emptying and increased gastric responsiveness in vitro. These phenomena were prevented by subdiaphragmatic vagotomy and by atenolol and win 55,212-2 treatments, showing vagal involvement of ß1-adrenergic and cannabinoid CB1/CB2 receptors.

Plasma Lipid Profile and Systemic Inflammation in Patients With Cancer Cachexia.

Cancer cachexia affects about 80% of advanced cancer patients, it is linked to poor prognosis and to date, there is no efficient treatment or cure. The syndrome leads to progressive involuntary loss of muscle and fat mass induced by systemic inflammatory processes. The role of the white adipose tissue (WAT) in the onset and manifestation of cancer cachexia gained importance during the last decade. WAT wasting is not only characterized by increased lipolysis and release of free fatty acids (FFA), but in addition, owing to its high capacity to produce a variety of inflammatory factors. The aim of this study was to characterize plasma lipid profile of cachectic patients and to correlate the FA composition with circulating inflammatory markers; finally, we sought to establish whether the fatty acids released by adipocytes trigger and/or contribute to local and systemic inflammation in cachexia. The study selected 65 patients further divided into 3 groups: control (N); weight stable cancer (WSC); and cachectic cancer (CC). The plasma FA profile was significantly different among the groups and was positively correlated with pro-inflammatory cytokines expression in the CC patients. Therefore, we propose that saturated to unsaturated FFA ratio may serve as a means of detecting cachexia.

Role of Zinc in Zinc-α2-Glycoprotein Metabolism in Obesity: a Review of Literature.

Excessive adipose tissue promotes the manifestation of endocrine disorders such as reduction of the secretion of zinc-α2-glycoprotein (ZAG), an adipokine with anti-inflammatory and lipid-mobilizing activity. The molecular structure of this adipokine includes binding sites for zinc, a trace element with important antioxidant and immunological proprieties that also participates in energy metabolism and stimulates the function of ZAG. The objective of this review is to highlight current data on the metabolism of ZAG in obesity and the role of zinc in this process. The identified studies show that subjects with obesity have low serum concentrations of zinc and ZAG, as well as low expression of the genes encoding this protein. Thus, zinc appears to be an important regulator of the homeostasis of ZAG in the body; however, alterations in the metabolism of zinc in obesity appear to compromise the functions of ZAG. Therefore, further studies are needed to clarify the relationship between zinc and ZAG metabolism and its repercussions in obesity.

NF-κBp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients.

Cancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-κB). We have examined the gene expression of the subunits NF-κBp65 and NF-κBp50, as well as NF-κBp65 and NF-κBp50 binding, the gene expression of pro-inflammatory mediators under NF-κB control (IL-1ß, IL-6, INF-γ, TNF-α, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-κBp65 and its target genes expression (TNF-α, IL-1ß, MCP-1 and IκB-α) were significantly higher in cachectic cancer patients. Moreover, NF-κBp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-κB pathway plays a role in the promotion of WAT inflammation during cachexia.

Leucine improves protein nutritional status and regulates hepatic lipid metabolism in calorie-restricted rats.

Several studies have highlighted the potential of leucine supplementation for the treatment of metabolic diseases including type 2 diabetes and obesity. Caloric restriction is a common approach to improve the health in diabetic and obese subjects. However, very few studies assessed the effects of leucine supplementation in calorie-restricted animals. Rats were subjected to a 30% calorie-restricted diet for 6 weeks to study the effects of leucine supplementation on protein status markers and lipid metabolism. Caloric restriction reduced the body weight. However, increased leucine intake preserved body lean mass and protein mass and improved protein anabolism as indicated by the increased circulating levels of albumin and insulin-like growth factor-1 (IGF-1), and the liver expression of albumin and IGF-1 messenger RNA. Leucine supplementation also increased the circulating levels of interleukin-6 and leptin but did not affect the tumour necrosis factor-α and monocyte chemotactic protein-1 concentrations. Ketone bodies were increased in rats consuming a leucine-rich diet, but we observed no changes in cholesterol or triglycerides concentrations. Caloric restriction reduced the liver expression of peroxisome proliferator activated receptor-α and glucose-6-phosphatase, whereas leucine supplementation increased the liver expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA) reductase and sterol regulatory element-binding transcription factor 1. A leucine-rich diet during caloric restriction preserved whole body protein mass and improved markers of protein anabolism. In addition, leucine modulated the hepatic lipid metabolism. These results indicate that increased leucine intake may be useful in preventing excessive protein waste in conditions of large weight loss.