Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer

AbstractAdipocytes promote progression of multiple cancers, but their role in pancreatic intraepithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC) is poorly defined. Nutrient transfer is a mechanism underlying stromal cell-cancer crosstalk. We studied the role of adipocytes in regulating in vitro PanIN and PDAC cell proliferation with a focus on glutamine metabolism. Murine 3T3L1 adipocytes were used to model adipocytes. Cell lines derived from PKCY mice were used to model PanIN and PDAC. Co-culture was used to study the effect of adipocytes on PanIN and PDAC cell proliferation in response to manipulation of glutamine metabolism. Glutamine secretion was measured with a bioanalyzer. Western blotting was used to study the effect of PanIN and PDAC cells on expression of glutamine-related enzymes in adipocytes. Adipocytes promote proliferation of PanIN and PDAC cells, an effect that was amplified in nutrient-poor conditions. Adipocytes secrete glutamine and rescue PanIN and PDAC cell proliferation in the absence of glutamine, an effect that was glutamine synthetase-dependent and involved PDAC cell-induced down-regulation of glutaminase expression in adipocytes. These findings suggest glutamine transfer as a potential mechanism underlying adipocyte-induced PanIN and PDAC cell proliferation

Depot-specific adipocyte-extracellular matrix metabolic crosstalk in murine obesity

Subcutaneous (SAT) and visceral (VAT) adipose tissues have distinct metabolic phenotypes. We hypothesized that the extracellular matrix (ECM) regulates depot-specific differences in adipocyte metabolic function in murine obesity. VAT and SAT preadipocytes from lean or obese mice were subject to adipogenic differentiation in standard 2D culture on plastic tissue culture plates or in 3D culture in ECM, followed by metabolic profiling. Adipocytes from VAT relative to SAT manifested impaired insulin-stimulated glucose uptake and decreased adipogenic capacity. In 3D-ECM-adipocyte culture, ECM regulated adipocyte metabolism in a depot-specific manner, with SAT ECM rescuing defects in glucose uptake and adipogenic gene expression in VAT adipocytes, while VAT ECM impaired adipogenic gene expression in SAT adipocytes. These findings demonstrate that ECM-adipocyte crosstalk regulates depot-specific differences in adipocyte metabolic dysfunction in murine obesity

Matrix density regulates adipocyte phenotype

ABSTRACTAlterations of the extracellular matrix contribute to adipose tissue dysfunction in metabolic disease. We studied the role of matrix density in regulating human adipocyte phenotype in a tunable hydrogel culture system. Lipid accumulation was maximal in intermediate hydrogel density of 5 weight %, relative to 3% and 10%. Adipogenesis and lipid and oxidative metabolic gene pathways were enriched in adipocytes in 5% relative to 3% hydrogels, while fibrotic gene pathways were enriched in 3% hydrogels. These data demonstrate that the intermediate density matrix promotes a more adipogenic, less fibrotic adipocyte phenotype geared towards increased lipid and aerobic metabolism. These observations contribute to a growing literature describing the role of matrix density in regulating adipose tissue function

LUMICAN MODULATES ADIPOCYTE FUNCTION IN OBESITY-ASSOCIATED TYPE 2 DIABETES

Obesity-associated type 2 diabetes (DM) leads to adipose tissue dysfunction. Lumican is a proteoglycan implicated in obesity, insulin resistance (IR), and adipocyte dysfunction. Using human visceral adipose tissue (VAT) from subjects with and without DM, we studied lumican effects on adipocyte function. Lumican was increased in VAT and adipocytes in DM. Lumican knockdown in adipocytes decreased lipolysis and improved adipogenesis and insulin sensitivity in VAT adipocytes in DM, while treatment with human recombinant lumican increased lipolysis and impaired insulin-sensitivity in an ERK-dependent manner. We demonstrate that lumican impairs adipocyte metabolism, partially via ERK signaling, and is a potential target for developing adipose tissue-targeted therapeutics in DM.</p

Matrix density regulates adipocyte phenotype

Alterations of the extracellular matrix contribute to adipose tissue dysfunction in metabolic disease. We studied the role of matrix density in regulating human adipocyte phenotype in a tunable hydrogel culture system. Lipid accumulation was maximal in intermediate hydrogel density of 5 weight %, relative to 3% and 10%. Adipogenesis and lipid and oxidative metabolic gene pathways were enriched in adipocytes in 5% relative to 3% hydrogels, while fibrotic gene pathways were enriched in 3% hydrogels. These data demonstrate that the intermediate density matrix promotes a more adipogenic, less fibrotic adipocyte phenotype geared towards increased lipid and aerobic metabolism. These observations contribute to a growing literature describing the role of matrix density in regulating adipose tissue function.</p

Adipose tissue fibrosis, hypertrophy, and hyperplasia: Correlations with diabetes in human obesity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/117485/1/oby21377_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/117485/2/oby21377.pd

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data