Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women

Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome

Steric and electronic properties of N-heterocyclic carbenes (NHC) : a detailed study on their interaction with Ni(CO)4

N-heterocyclic carbene ligands IMes (1), SIMes (2), IPr (3), SIPr (4), and lCy (5) react with Ni(CO)(4) to give the saturated tricarbonyl complexes Ni(CO)(3)(IMes) (8), Ni(CO)(3)(SIMes) (9), Ni(CO)(3)(IPr) (10), Ni(CO)(3)(SIPr) (11), and Ni(CO)(3)(ICy) (12), respectively. The electronic properties of these complexes have been compared to their phosphine analogues of general formula Ni(CO)(3)(PR3) by recording their v(CO) stretching frequencies. While all of these NHCs are better donors than tertiary phosphines, the differences in donor properties between ligands 1-5 are surprisingly small. Novel, unsaturated Ni(CO)(2)(IAd) (13) and Ni(CO)(2)((IBu)-Bu-t) (14) compounds are obtained from the reaction of Ni(CO)(4) with IAd (6) and (IBu)-Bu-t (7). Complexes 13 and 14 are highly active toward substitution of the NHC as well as the carbonyl ligands. This has allowed the determination of Ni-C(NHC) bond dissociation energies and the synthesis of various unsaturated Ni(0) and Ni(II) complexes. Computational studies on compounds 8-14 are in line with the experimental findings and show that IAd (6) and (IBu)-Bu-t (7) are more bulky than IMes (1), SIMes (2), IPr (3), SIPr (4), and lCy (5). Furthermore, a method based on %V-bur values has been developed for the direct comparison of steric requirements of NHCs and tertiary phosphines. Complexes 8-14, as well as NiCl(C3H5)((IBu)-Bu-t) (16) and NiBr(C3H5)((IBu)-Bu-t) (17), have been characterized by X-ray crystallography

Steric and electronic properties of N-heterocyclic carbenes (NHC): A detailed study on their interaction with Ni(CO)(4)

N-heterocyclic carbene ligands IMes (1), SIMes (2), IPr (3), SIPr (4), and lCy (5) react with Ni(CO)(4) to give the saturated tricarbonyl complexes Ni(CO)(3)(IMes) (8), Ni(CO)(3)(SIMes) (9), Ni(CO)(3)(IPr) (10), Ni(CO)(3)(SIPr) (11), and Ni(CO)(3)(ICy) (12), respectively. The electronic properties of these complexes have been compared to their phosphine analogues of general formula Ni(CO)(3)(PR3) by recording their v(CO) stretching frequencies. While all of these NHCs are better donors than tertiary phosphines, the differences in donor properties between ligands 1-5 are surprisingly small. Novel, unsaturated Ni(CO)(2)(IAd) (13) and Ni(CO)(2)((IBu)-Bu-t) (14) compounds are obtained from the reaction of Ni(CO)(4) with IAd (6) and (IBu)-Bu-t (7). Complexes 13 and 14 are highly active toward substitution of the NHC as well as the carbonyl ligands. This has allowed the determination of Ni-C(NHC) bond dissociation energies and the synthesis of various unsaturated Ni(0) and Ni(II) complexes. Computational studies on compounds 8-14 are in line with the experimental findings and show that IAd (6) and (IBu)-Bu-t (7) are more bulky than IMes (1), SIMes (2), IPr (3), SIPr (4), and lCy (5). Furthermore, a method based on %V-bur values has been developed for the direct comparison of steric requirements of NHCs and tertiary phosphines. Complexes 8-14, as well as NiCl(C3H5)((IBu)-Bu-t) (16) and NiBr(C3H5)((IBu)-Bu-t) (17), have been characterized by X-ray crystallography.</p