The Action of Vitamin D in Adipose Tissue: Is There the Link between Vitamin D Deficiency and Adipose Tissue-Related Metabolic Disorders?

Adipose tissue plays an important role in systemic metabolism via the secretion of adipocytokines and storing and releasing energy. In obesity, adipose tissue becomes dysfunctional and characterized by hypertrophied adipocytes, increased inflammation, hypoxia, and decreased angiogenesis. Although adipose tissue is one of the major stores of vitamin D, its deficiency is detective in obese subjects. In the presented review, we show how vitamin D regulates numerous processes in adipose tissue and how their dysregulation leads to metabolic disorders. The molecular response to vitamin D in adipose tissue affects not only energy metabolism and adipokine and anti-inflammatory cytokine production via the regulation of gene expression but also genes participating in antioxidant defense, adipocytes differentiation, and apoptosis. Thus, its deficiency disturbs adipocytokines secretion, metabolism, lipid storage, adipogenesis, thermogenesis, the regulation of inflammation, and oxidative stress balance. Restoring the proper functionality of adipose tissue in overweight or obese subjects is of particular importance in order to reduce the risk of developing obesity-related complications, such as cardiovascular diseases and diabetes. Taking into account the results of experimental studies, it seemed that vitamin D may be a remedy for adipose tissue dysfunction, but the results of the clinical trials are not consistent, as some of them show improvement and others no effect of this vitamin on metabolic and insulin resistance parameters. Therefore, further studies are required to evaluate the beneficial effects of vitamin D, especially in overweight and obese subjects, due to the presence of a volumetric dilution of this vitamin among them.

Skate-Skin Mucin, Rich in Sulfated Sugars and Threonine, Promotes Proliferation of Akkermansia muciniphila in Feeding Tests in Rats and In Vitro Fermentation Using Human Feces

Dietary factors, affect Akkermansia muciniphila (AM) abundance in the colon, have attracted attention, driven by the inverse correlation between AM abundance and metabolic disorders. We prepared skate-skin mucin (SM), porcine stomach mucin (PM), and rat gastrointestinal mucin (RM). SM contained more sulfated sugars and threonine than PM or RM. Rats were fed a control diet or diets including SM, PM, or RM (15 g/kg), or SM (12 g/kg) from five different threonine contents for 14 d. Cecal total bacteria and AM were less and more numerous, respectively, in SM-fed rats than the others, but SM did not affect microbial species-richness. Low-threonine SM did not induce AM proliferation. The in vitro fermentation with human feces showed that the rate of AM increase was greater with SM than PM. Collectively, heavy SM sulfation facilitates a priority supply of SM-derived amino sugars and threonine that promotes AM proliferation in rats and human feces.

Jatrorrhizine: A Review of Sources, Pharmacology, Pharmacokinetics and Toxicity

Jatrorrhizine, an isoquinoline alkaloid, is a bioactive metabolite in common medicinal plants, such as Berberis vernae Schneid., Tinospora sagittata (Oliv.) Gagnep. and Coptis chinensis Franch. These plants have been used for centuries in traditional medicine for their wide-ranging pharmacological properties. This review emphasizes the latest and comprehensive information on the sources, pharmacology, pharmacokinetics and toxicity of jatrorrhizine. Studies on this alkaloid were collected from scientific internet databases, including the Web of Science, PubMed, ScienceDirect, Google Scholar, Elsevier, Springer, Wiley Online Library and Europe PMC and CNKI, using a combination of keywords involving “jatrorrhizine”, “sources”, “pharmacology,” “pharmacokinetics,” and “toxicology”. Jatrorrhizine exhibits anti-diabetic, antimicrobial, antiprotozoal, anticancer, anti-obesity and hypolipidemic properties, along with central nervous system activities and other beneficial activity. Studies of jatrorrhizine have laid the foundation for its application to the treatment of various diseases, but some issues still exist. Further investigations might emphasize 1) specific curative mechanisms of jatrorrhizine and clinical utility, 2) application prospect in the treatment of metabolic disorders, 3) comprehensive investigations of the toxicity mechanisms and 4) interactions of jatrorrhizine with other pharmaceuticals and development of derivatives.

Heterogeneity of abdominal obesity in patients with cardiovascular diseases

Aim: To assess the content of visceral adipose tissue (VAT) in patients with abdominal obesity and its relationship with metabolic disorders.Material and methods. Patients with abdominal obesity (n=107) were included in the study. All participants had an assessment of anthropometric parameters (height, weight), calculation of body mass index (BMI), proportion of total adipose tissue and VAT (bioimpedance analyzer), high-density lipoprotein cholesterol (HDL-c) levels, triglycerides, fasting blood glucose, epicardial thickness adipose tissue (two-dimensional echocardiography).Results. The median share of VAT (bioimpedance method) was 13%. Patients with abdominal obesity are divided by VAT into 2 groups: ≥14% or ≤13%. Patients with VAT≥14% had significantly higher levels of triglycerides (1.76 [1.27; 2.38] mmol / L) and glucose (6.33 [5.78; 7.87] mmol / L), and below HDL-c levels (0.95 [0.85; 1.21] mmol / L) compared with patients with VAT≤13% (1.32 [1.02; 1.50], 5.59 [5, 11; 6.16] and 1.31 [1.07; 1.58] mmol / L, respectively; p<0.001 for all three comparisons). A significant correlation was found between VAT and triglyceride, glucose and HDL-c levels (r=0.40; r=0.40; r=-0.31, respectively; p<0.001).Conclusion. Persons with abdominal obesity are heterogeneous in the proportion of VAT. The proportion of VAT above the median is associated with metabolic disorders that are significant for the development and progression of atherosclerosis. An increase in BMI in obese individuals is not associated with an increase in VAT and an increase in the severity of metabolic disorders.

Spectrum Analysis of Inherited Metabolic Disorders for Expanded Newborn Screening in a Central Chinese Population

Neonatal inherited metabolic disorders (IMDs) are closely associated with early neonatal death and abnormal growth and development. Increasing attention has been paid to IMDs because of their high incidence and diversity. However, there are no reports about the incidence of IMDs in Changsha, China. Therefore, we retrospectively analyzed the screening results of neonates to evaluate the characteristics of IMDs in the area. From January 2016 to December 2020, 300,849 neonates were enrolled for expanded newborn screening by tandem mass spectrometry in the Neonatal Disease Screening Center of the Changsha Hospital for Maternal &amp; Child Health Care. Newborns with mild initial results were recalled for repeated tests; if the second test was still positive, the patient was referred for confirmatory tests. A total of 71 confirmed cases were identified in our study, with an incidence rate of 1:4,237. There were 28 cases of amino acid metabolic disorders, representing 39.44% of the IMDs diagnosed, with an incidence rate of 1:10,745. Twelve newborns were diagnosed with organic acid metabolic disorders, accounting for 16.66% of IMDs, with an incidence rate of 1:25,071. There were 31 cases of fatty acid oxidation disorders, representing 43.05% of IMDs, with an incidence rate of 1:9,705. Overall, 14 types of IMDs were found in Changsha. The most common disorders in the region were primary carnitine deficiency, hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase deficiency. Their incidence rate is respectively 1:13,675, 1:16,714 and 1:42,978. The mutations in PAH, SLC22A5, and ACADS are the leading causes of IMDs in this area. This study demonstrates the importance of utilizing MS/MS in IMD screening for early diagnosis and treatment. This strategy may be used for prenatal genetic counseling to avoid irreversible growth and intellectual development disorders in children.

Lysine Acetylation, Cancer Hallmarks and Emerging Onco-Therapeutic Opportunities

Acetylation, a reversible epigenetic process, is implicated in many critical cellular regulatory systems including transcriptional regulation, protein structure, activity, stability, and localization. Lysine acetylation is the most prevalent and intensively investigated among the diverse acetylation forms. Owing to the intrinsic connections of acetylation with cell metabolism, acetylation has been associated with metabolic disorders including cancers. Yet, relatively little has been reported on the features of acetylation against the cancer hallmarks, even though this knowledge may help identify appropriate therapeutic strategies or combinatorial modalities for the effective treatment and resolution of malignancies. By examining the available data related to the efficacy of lysine acetylation against tumor cells and elaborating the primary cancer hallmarks and the associated mechanisms to target the specific hallmarks, this review identifies the intrinsic connections between lysine acetylation and cancer hallmarks and proposes novel modalities that can be combined with HDAC inhibitors for cancer treatment with higher efficacy and minimum adverse effects.