Biology subjects

Brown, L. H.

Publications and source records attributed to Brown, L. H..

4 recordsLinked to original sources

bioRxiv2025

DHA Increases Angptl4 Gene Expression and Reduces LPL Activity in a PPARγ-dependent manner in Adipocytes

Omega-3 polyunsaturated fatty acids (N-3 PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are well recognized for their triacylglycerol (TAG)-lowering properties. These effects are generally attributed to reduced hepatic lipogenesis and increased {beta}-oxidation; however, the contribution of white adipose tissue (WAT) towards the hypotriglyceridemic properties of N-3 PUFA is less defined. Lipoprotein lipase (LPL) regulates TAG hydrolysis to influence fatty acid uptake into WAT, a process that can be inhibited by angiopoietin-like 4 (ANGPTL4). When re-examining a previous mouse study, we found that mice consuming a diet rich in EPA/DHA had increased WAT Angptl4 expression in the fasted state compared to a control diet. Therefore, the goal of this study was to explore the role of N-3 PUFA on the regulation of Angptl4 expression and LPL activity in mouse adipocytes. 3T3-L1 adipocytes treated with DHA (100M), but not ALA or EPA, increased Angptl4 expression and reduced LPL activity similar to that observed with a PPAR{gamma} agonist (pioglitazone). When Ppar{gamma} expression was knocked down with siRNA, the ability of DHA and pioglitazone to induce Angptl4 expression was ablated. Further, DHA- and pioglitazone-induced reductions in LPL activity were mitigated when Angptl4 expression was silenced. Taken together, these results suggest that DHA regulates LPL activity by increasing Angptl4 expression in a PPAR{gamma}-dependent manner. Our results have uncovered a novel mechanism by which DHA regulates ANGPTL4 to influence LPL-mediated hydrolysis of circulating TAG in adipocytes. Future in-vivo studies are necessary to determine the relevance of DHA regulation of ANGPTL4 towards whole-body lipid homeostasis and cardiometabolic health. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/685896v2_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@75505dorg.highwire.dtl.DTLVardef@1ef29b4org.highwire.dtl.DTLVardef@9aec7dorg.highwire.dtl.DTLVardef@11c372b_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDHA increases Angptl4 gene expression and reduces LPL activity in 3T3-L1 adipocytes C_LIO_LIChanges in FOXO1 do not explain DHA-induced changes in Angptl4 gene expression C_LIO_LISilencing Ppar{gamma} ablates DHA-induced increases in Angptl4 gene expression C_LIO_LISilencing Angptl4 partially attenuates DHA-induced reductions in LPL activity C_LI

cell biology↗

bioRxiv2025

Phased Potato Genome Assembly and Association Genetics Enable Characterisation of the Elusive H1 Resistance Locus Against Potato Cyst Nematodes

The complexity of potato genetics, characterised by tetrasomic inheritance, has contributed to slower genetic gain in potato compared to other major crops. Disease resistance genes, often found in large clusters of highly similar paralogs and alleles, further complicate genetic studies. The H1 resistance locus, introgressed into potato cultivars from Solanum tuberosum spp. andigena, has been successfully used for over 60 years to control Globodera rostochiensis in Europe. Although previous genetic studies mapped this resistance to chromosome 5, the complete structure of the locus remained elusive. To reduce genomic complexity, we generated a dihaploid of the cultivar Athlete, DH4_Athlete, carrying the H1 resistance locus, and produced a phased haplotype representation of the H1 interval using Oxford Nanopore sequencing. Combined with RenSeq-based association genetics, this approach allowed us to reconstruct the entire H1 locus, including recombination points at both the 5' and 3' ends of the interval.

plant biology↗

bioRxiv2022

SMRT-AgRenSeq-d in potato (Solanum tuberosum) identifies candidates for the nematode resistance Gpa5

Potato is the third most important food crop in the world. Diverse pathogens threaten sustainable crop production but can be controlled, in many cases, through the deployment of disease resistance genes belonging to the family of nucleotide-binding, leucine-rich-repeat (NLR) genes. To identify functional NLRs in established varieties, we have successfully established SMRT-AgRenSeq in tetraploid potatoes and have further enhanced the methodology by including dRenSeq in an approach that we term SMRT-AgRenSeq-d. The inclusion of dRenSeq enables the filtering of candidates after the association analysis by establishing a presence/absence matrix across resistant and susceptible potatoes that is translated into an F1 score. Using a SMRT-RenSeq based sequence representation of the NLRome from the cultivar Innovator, SMRT-AgRenSeq-d analyses reliably identified the late blight resistance benchmark genes R1, R2-like, R3a and R3b in a panel of 117 varieties with variable phenotype penetrations. All benchmark genes were identified with an F1 score of 1 which indicates absolute linkage in the panel. When applied to the elusive nematode disease resistance gene Gpa5 that controls the Potato Cyst Nematode (PCN) species Globodera pallida (pathotypes Pa2/3), SMRT-AgRenSeq-d identified nine strong candidates. These map to the previously established position on potato chromosome 5 and are potential homologs of the late blight resistance gene R1. Assuming that NLRs are involved in controlling many types of resistances, SMRT-AgRenSeq-d can readily be applied to diverse crops and pathogen systems. In potato, SMRT-AgRenSeq-d lends itself, for example, to further study the elusive PCN resistances H1 or H3 for which phenotypic data exist.

plant biology↗

bioRxiv2021

A genome-annotated bacterial collection of the barley rhizosphere microbiota

We generated a bacterial collection from the rhizosphere of cultivated barley (Hordeum vulgare L. ssp. vulgare) to assess taxonomic distribution of culturable members of the barley microbiota and their plant growth-promoting potential. From this we retrieved strains belonging to the dominant phyla of the plant microbiota-- Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria--and gathered evidence they code for functional genes implicated in nitrogen fixation, hydrogen cyanide channels and phosphate solubilisation. Here we present an initial comparative genomic analysis of the collection revealing that plant growth-promoting potential of the culturable barley bacterial microbiota appears to have a relatively broad phylogenetic base while retaining some strain-specificity.

microbiology↗