Intramuscular fat (IMF) content affects meat quality and varies in different pig breeds. However, the underlying mechanisms of different IMF depositions in different genetic backgrounds of pigs have not been fully elucidated as yet. Lipid metabolism theoretically contributes to the variation of IMF content. The expression levels of genes and proteins as well as enzyme activities implicated in muscle lipid metabolism were investigated, which included lipogenetic genes (SREBP-1c and FAS), fatty acid transporting genes (H-FABP and A-FABP), fatty acid oxidative gene (CPT-1B) and lipolytic genes (ATGL and HSL) as well as the desaturated fatty acid gene (SCD). Longissimus muscle samples were collected from fatty Wujin pigs and lean Landrace pigs. Results showed that the average daily gain of Wujin pigs was lower than that of Landrace pigs. Wujin pigs had greater adipocyte diameter, IMF content and PUFA percentage than that of Landrace pigs. Compared with Landrace pigs, Wujin pigs exhibited higher expression levels, both in mRNA and protein, of FAS, SREBP-1c, SCD, A-FABP and H-FABP genes and lower expression levels of CPT-1B, HSL and ATGL genes. Overall, Wujin pigs possessed higher mRNA abundance, protein expression or enzyme activities of anabolism, fatty acid transportation and desaturation, and lower catabolism. Therefore, the mechanism of higher IMF content in fatty pigs may be due to the higher capacity of lipogenesis and fatty acid transportation and the lower capacity of lipolysis.
Kosinostatin (KST), an antitumor antibiotic, features a pyrrolopyrrole moiety spirally jointed to a five-membered ring of an anthraquinone framework glycosylated with a γ-branched octose. By a combination of in silico analysis, genetic characterization, biochemical assay, and precursor feeding experiments, a biosynthetic pathway for KST was proposed, which revealed (1) the pyrrolopyrrole moiety originates from nicotinic acid and ribose, (2) the bicyclic amidine is constructed by a process similar to the tryptophan biosynthetic pathway, and (3) a discrete adenylation enzyme and a peptidyl carrier protein (PCP) are responsible for producing a PCP-tethered building block parallel to type II polyketide synthase (PKS) rather than for the PKS priming step by providing the starter unit. These findings provide an opportunity to further explore the inexplicable enzymatic logic that governs the formation of pyrrolopyrrole moiety and the spirocyclic skeleton.
Increasing studies have shown that obesity is the primary cause of cardiovascular diseases, non-alcoholic fatty liver diseases, type 2 diabetes, and a variety of cancers. The dysfunction of gut microbiota was proved to result in obesity. Recent research indicated ANGPTL4 was a key regulator in lipid metabolism and a circulating medium for gut microbiota and fat deposition. The present study was conducted to investigate the alteration of gut microbiota and ANGPTL4 expression in the gastrointestinal tract of mice treated by the high-fat diet. Ten C57BL/6J mice were randomly allocated to two groups and fed with a high-fat diet (HFD) containing 60% fat or a normal-fat diet (Control) containing 10% fat. The segments of ileum and colon were collected for the determination of ANGPTL4 expression by RT-qPCR and immunohistochemical analysis while the ileal and colonic contents were collected for 16S rRNA gene sequencing. The results showed HFD significantly increased mice body weight, epididymal fat weight, perirenal fat weight, liver weight, and the lipid content in the liver (P < 0.05). The relative expression of ANGPTL4 and the ANGPTL4-positive cells in the ileum and colon of mice was significantly increased by HFD treatment. Furthermore, 16S rRNA gene sequencing of the ileal and colonic microbiota suggested that HFD treatment changed the composition of the gut microbiota. The ratio of Firmicutes to Bacteroidetes and the abundance of Allobaculum was significantly higher in the HFD group than in the Control group while the abundance of Adlercreutzia, Bifidobacterium, Prevotellaceae UCG-001, and Ruminococcus was significantly decreased. Interestingly, the abundance of Allobaculum was positively correlated with the expression of ANGPTL4. These findings provide a theoretical foundation for the development of strategies to control the obesity and related diseases by the regulation of ANGPTL4 and gut microbiota.
Graphical Abstract In the decade since the discovery of englerin A (1) and its potent activity in cancer models, this natural product and its analogues have been the subject of numerous chemical, biological, and preclinical studies by many research groups. This review summarizes published findings and proposes further research directions required for entry of an englerin analogue into clinical trials for kidney cancer and other conditions.
A convenient and practical hydrosulfonylation and disulfonylation of substituted maleimides was realized using sulfonyl hydrazides as the sulfur reagent and tert-butyl hydroperoxide as the oxidant. The advantages of the reactions include mild and transition-metal-free reaction conditions, good functional group tolerance, and readily available starting materials. The radical species-induced pathway is also demonstrated by mechanistic studies.
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