New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women

<p>Abstract</p> <p>Background</p> <p>Vaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines.</p> <p>Design</p> <p>We analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI ≥ 40 kg/m²] and 31 lean [BMI ≤ 25]). We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR.</p> <p>Results</p> <p>Serum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue.</p> <p>Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS). Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls.</p> <p>Conclusions</p> <p>The present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women.</p

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Sphingolipid synthesis and metabolism as a target for anti Giardial therapy

Giardia lamblia, a parasitic protozoan and a major cause of waterborne enteric disease worldwide, exists in two morphologic forms: (1) the infective trophozoite, and (2) the transmissible water-resistant cyst. Exposure of cysts to gastric acid during passage through the human stomach triggers excystation, while factors in the small intestine, where trophozoites colonize, induce encystation or cyst formation. Successful operation of this excystation-encystation cycle is important for this pathogen to survive, multiply, and differentiate in the human small intestine. Sphingolipids and their metabolites have been shown to modulate a wide variety of cellular events, including apoptosis, cell signaling, and synthesis of membrane rafts. More recently, 3-keto-sphinganine, synthesized by serine-palmitoyl transferase (SPT) as the first product of sphingolipid biosynthesis, was shown to be involved in endocytosis in yeast. Interestingly, however, Giardia has a very limited ability to synthesize sphingolipids de novo and depends on exogenous sources for energy production and other metabolic activities. I hypothesize that sphingolipids scavenged by this parasite from its micro-environment or synthesized de novo (although this is limited) play key roles in regulating the life cycle of Giardia. To test my hypothesis, I used radioactive and fluorescent sphingolipid probes and various metabolic/pathway inhibitors to study the mechanism of sphingolipid internalization and targeting. Studies indicated that Giardia trophozoites have the ability to internalize and target intracellular ceramide, the major sphingolipid precursor, through clathrin- and cytoskeleton-based endocytic pathways. I speculated that this parasitic protozoan has evolved cytoskeletal and clathrin-dependent endocytic mechanisms for importing ceramide and sphigomyelin molecules from the cell exterior for the synthesis of membranes and vesicles during growth and differentiation. In the second phase of my investigation, I used molecular and bioinformatic approaches to analyze sphingolipid metabolic genes in Giardia. Analyses revealed that within all sphingolipid biosynthesis pathways only five gene transcripts---serine-palmitoyltransferase 1 & 2 (spt-1 and 2), ceramide-glucosyltransferase (glcT-1), and sphingomyelinase B & 3b (smase b and 3b)---are differentially expressed in trophozoites and encysting cells. The spt-1 and spt-2 genes are expressed predominately in trophozoites, while glcT-1 and smase mRNAs are increased in encysting cells. Phylogenic and protein-family (Pfam) databases have indicated that genes for both SPT subunits (i.e., spt-1 and 2) in Giardia are closely related to prokaryotic amino acid transferases. Giardial glcT-1, on the other hand, belongs to the glucosyltransferase family 2 that is distributed widely in prokaryotes and eukaryotes. To test whether these genes and gene products are important for the growth and encystation of this waterborne pathogen, I used L-cycloserine (SPT inhibitor) and two newly available GlcT-1 inhibitors--- D-threo-1-phenyl-2-decanoyl-3-morpholinopropanol (PDMP) and D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP)---on trophozoite and encysting cells. The results suggested that the inhibition of SPT by L-cycloserine induced morphological alterations and inhibited the endocytosis and intracellular targeting of fluorescently labeled ceramide dramatically, suggesting that the product of SPT enzyme (i.e., 3-keto-sphinganine) is in fact regulated the endocytosis in Giardia, as in Saccharomyces cerevisiae. On the other hand, PDMP and PPMP, two inhibitors of GlcT-1, reduced the production of vitro-derived cysts and damaged the cyst wall structures, as evidenced by DIC/confocal microscopy. These studies suggest that sphingolipids are important for giardial growth and encystation and that they could serve as potential targets for developing new therapies against Giardia and related mucosal parasites