Biology subjects

Ma, R. C.

Publications and source records attributed to Ma, R. C..

4 recordsLinked to original sources

bioRxiv2022

Higher habitual FODMAP intake is associated with lower body mass index, lower insulin resistance and higher short-chain fatty acid-producing microbiota in people with prediabetes

Aims/hypothesisThe quantity and quality of FODMAPs can alter the relative abundance of gut microbiota with metabolic consequences although similar data are lacking in people with prediabetes. We investigated associations between habitual FODMAP contents, gut microbiota and glucose/insulin responses in subjects with prediabetes. MethodsIn this prospective cross-sectional study, ninety-eight subjects with impaired glucose tolerance (IGT) (mean age: 57{+/-}7 years, 43 % men) had assessment of body composition, 6-point oral glucose tolerance tests (OGTT), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and 3-day dietary intake. We analysed faecal samples in a sub-group of 20 subjects with IGT and 10 subjects with normal glucose tolerance by 16S rRNA microbiome analysis. ResultsObese subjects with IGT had the lowest daily FODMAP intake compared with their non-overweight and non-obese counterparts (5.7 (3.9-7.9) vs 7.1 (5.0-11.3) vs 9.9 (4.1-22.4) g/day, p=0.024) despite having similar total daily energy intake. Total content of FODMAPs was negatively correlated with body fat. After adjustment for age and gender, total FODMAPs were negatively associated with BMI and HOMA-IR. This remained significant after adjustment for macronutrients and physical activity (p=0.032 and p=0.036 respectively). FODMAP contents were strongly associated with short-chain fatty acid (SCFA)-producing bacteria, such as Lactobacillus (p=0.011), Akkermansia muciniphila (p=0.012), and Bifidobacterium longum (p=0.010), the abundance of which were negatively correlated with 2-hr plasma glucose (r = -0.524, p =0.003). ConclusionIn individuals with IGT, higher habitual FODMAP intake was associated with lower body fat and insulin resistance and increased abundance of SCFA-producing bacteria, calling for interventional studies to evaluate the effects of FODMAP intake in prediabetes.

microbiology↗

bioRxiv2022

Identifying human islet microRNAs associated with donor sex, age and body mass index

ObjectivesHuman islets are widely researched to understand pathophysiological mechanisms leading to diabetes. Sex, age, and body mass index (BMI) are key donor traits influencing insulin secretion. Islet function is also regulated by an intricate network of microRNAs. MethodsHere, we profiled 754 microRNAs and 58,190 potential targets in up to 131 different human islet donor preparations (without diabetes) and assessed their association with donor traits. We further performed mechanistical studies to observe the causal role of the age-associated key microRNAs on relative telomere length in human islets. ResultsMicroRNA discovery analyses identified miR-199a-5p and miR-214-3p associated with sex, age and BMI; miR-147b with sex and age; miR-378a-5p with sex and BMI; miR-542-3p, miR-34a-3p, miR-34a-5p, miR-497-5p and miR-99a-5p with age and BMI. There were 959 mRNA transcripts associated with sex (excluding those from sex-chromosomes), 940 with age and 418 with BMI. MicroRNA-199a-5p and miR-214-3p levels inversely associate with transcripts critical in islet function, metabolic regulation, and senescence. Our functional studies verified that inhibition of these two microRNAs (miR-199a-5p/-214-3p) slowed down telomere length shortening in human islet cells maintained in vitro and demonstrating cellular senescence. ConclusionsOur analyses identify human islet cell microRNAs influenced by donor traits. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/512222v2_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1666c2org.highwire.dtl.DTLVardef@b4695forg.highwire.dtl.DTLVardef@720e99org.highwire.dtl.DTLVardef@1c78ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Local signaling specifies tissue-resident fibroblasts from multipotent sclerotome progenitors in zebrafish

Fibroblasts play an important role in maintaining tissue integrity by secreting components of the extracellular matrix and initiating response to injury. Although the function of fibroblasts has been extensively studied in adults, the embryonic origin and diversification of different fibroblast subtypes during development remain largely unexplored. Using zebrafish as a model, we show that the sclerotome, a sub-compartment of the somite, is the embryonic source of multiple fibroblast subtypes including tenocytes (tendon fibroblasts), blood vessel associated fibroblasts, fin mesenchymal cells, and interstitial fibroblasts. High-resolution imaging shows that different fibroblast subtypes occupy unique anatomical locations with distinct morphologies. Long-term Cre-mediated lineage tracing reveals that the sclerotome also contributes to cells closely associated with the axial skeleton. Ablation of sclerotome progenitors results in extensive skeletal defects. Using photoconversion-based cell lineage analysis, we find that sclerotome progenitors at different dorsal-ventral and anterior-posterior positions display distinct differentiation potentials. Single-cell clonal analysis combined with in vivo imaging suggests that the sclerotome mostly contains unipotent and bipotent progenitors prior to cell migration, and the fate of their daughter cells is biased by their migration paths and relative positions. Together, our work demonstrates that the sclerotome is the embryonic source of trunk fibroblasts as well as the axial skeleton, and local signals likely contribute to the diversification of distinct fibroblast subtypes.

developmental biology↗

bioRxiv2020

Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population of blood vessel associated cells. In contrast to pericytes, perivascular fibroblasts emerge early during development, express the extracellular matrix (ECM) genes col1a2 and col5a1, and display distinct morphology and distribution. Time-lapse imaging reveals that perivascular fibroblasts serve as pericyte precursors. Genetic ablation of perivascular fibroblasts results in dysmorphic blood vessels with variable diameters. Strikingly, col5a1 mutants show spontaneous hemorrhage, and the penetrance of the phenotype is strongly enhanced by the additional loss of col1a2. Together, our work reveals dual roles of perivascular fibroblasts in vascular stabilization where they establish the ECM around nascent vessels and function as pericyte progenitors. AUTHOR SUMMARYBlood vessels are essential to sustain life in humans. Defects in blood vessels can lead to serious diseases, such as hemorrhage, tissue ischemia, and stroke. However, how blood vessel stability is maintained by surrounding support cells is still poorly understood. Using the zebrafish model, we identify a new population of blood vessel associated cells termed perivascular fibroblasts, which originate from the sclerotome, an embryonic structure that is previously known to generate the skeleton of the animal. Perivascular fibroblasts are distinct from pericytes, a known population of blood vessel support cells. They become associated with blood vessels much earlier than pericytes and express several collagen genes, encoding main components of the extracellular matrix. Loss of perivascular fibroblasts or mutations in collagen genes result in fragile blood vessels prone to damage. Using cell tracing in live animals, we find that a subset of perivascular fibroblasts can differentiate into pericytes. Together, our work shows that perivascular fibroblasts play two important roles in maintaining blood vessel integrity. Perivascular fibroblasts secrete collagens to stabilize newly formed blood vessels and a sub-population of these cells also functions as precursors to generate pericytes to provide additional vascular support.

developmental biology↗