A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice
Kuipers, Eline N. ; Held, Ntsiki M. ; Het Panhuis, Wietse In; Modder, Melanie ; Ruppert, Philip M.M. ; Kersten, Sander ; Kooijman, Sander ; Guigas, Bruno ; Houtkooper, Riekelt H. ; Rensen, Patrick C.N. ; Boon, Mariëtte R. - \ 2019
American Journal of Physiology. Endocrinology and Metabolism 317 (2019)5. - ISSN 0193-1849 - p. E820 - E830.
brown adipose tissue - high-fat diet - lipid accumulation - macrophage - mitochondrial dynamics
Brown adipose tissue (BAT) catabolizes glucose and fatty acids to produce heat and thereby contributes to energy expenditure. Long-term high-fat diet (HFD) feeding results in so-called 'whitening' of BAT characterized by increased lipid deposition, mitochondrial dysfunction, and reduced fat oxidation. The aim of the current study was to unravel the rate and related mechanisms by which HFD induces BAT whitening and insulin resistance. Wild-type mice were fed a HFD for 0, 1, 3, or 7 days. Within 1 day of HFD, BAT weight and lipid content were increased. HFD also immediately reduced insulin-stimulated glucose uptake by BAT, indicating rapid induction of insulin resistance. This was accompanied by a tendency toward a reduced uptake of triglyceride-derived fatty acids by BAT. Mitochondrial mass and Ucp1 expression were unaltered, whereas after 3 days of HFD, markers of mitochondrial dynamics suggested induction of a more fused mitochondrial network. Additionally, HFD also increased macrophage markers in BAT after 3 days of HFD. Counterintuitively, the switch to HFD was accompanied by an acute rise in core body temperature. We showed that a single day of HFD feeding is sufficient to induce the first signs of whitening and insulin resistance in BAT, which reduces the uptake of glucose and triglyceride-derived fatty acids. BAT whitening and insulin resistance are likely sustained by reduced mitochondrial oxidation due to changes in mitochondrial dynamics and macrophage infiltration, respectively. Likely, the switch to HFD swiftly induces thermogenesis in other metabolic organs, which allows attenuation of BAT thermogenesis.
Bone marrow-specific caspase-1/11 deficiency inhibits atherosclerosis development in Ldlr-/- mice
Hendrikx, Tim ; Jeurissen, M.L.J. ; Gorp, P.J. Van; Gijbels, M.J. ; Walenbergh, S.M.A. ; Houben, Tom ; Gorp, Rick Van; Pöttgens, C.C. ; Stienstra, Rinke ; Netea, M.G. ; Hofker, M.H. ; Donners, M.M.P.C. ; Shiri-Sverdlov, Ronit - \ 2015
FEBS Journal 282 (2015)12. - ISSN 1742-464X - p. 2327 - 2338.
atherosclerosis - cardiovascular diseases - caspase-1/11 - inflammasome - macrophage
Recent investigations have suggested that inflammasome activation plays an important role during atherosclerosis. Upon activation, the inflammasome induces processing and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) via activation of caspase-1/11. Previously, it was shown that complete caspase-1 deficiency is protective against atherosclerosis development. However, while macrophages are the main inflammatory cells involved in atherosclerosis, the exact role of macrophage-specific caspase-1/11 activation during development of cardiovascular disease has never been investigated. We hypothesized that hematopoietic caspase-1/11 deficiency leads to reduced atherosclerosis development. To investigate the specific contribution of hematopoietic caspase-1/11 activation to atherosclerosis development, Ldlr-/- mice received a transplant (tp) of wild-type (WT) or caspase-1/11-/- bone marrow, to create WT-tp mice and caspase-1/11-/--tp mice, and fed a high-fat, high-cholesterol diet for 12 weeks. Our results showed an increase in anti-inflammatory blood leukocytes in caspase-1/11-/--tp mice compared with WT-tp mice, as indicated by a decreased level of Ly6Chigh monocytes and an increased level of Ly6Clow monocytes. In line with our hypothesis, hematopoietic deletion of caspase-1/11 resulted in a strong reduction in atherosclerotic plaque size. Furthermore, necrotic core content was dramatically decreased in caspase-1/11-/--tp mice. Our data indicate that hematopoietic caspase-1/11 activation is involved in vascular inflammation and atherosclerosis, and plays an important role in cardiovascular disease progression. In this study, we investigated the contribution of hematopoietic caspase-1/11 to atherosclerosis development by transferring wild-type or caspase-1/11 deficient bone marrow cells into hyperlipidemic Ldlr-/- recipient mice. Hematopoietic deletion of caspase-1/11 resulted in smaller plaque size and reduced cell death in the plaque area compared to controls. These data indicate that hematopoietic caspase-1/11 activation plays an important role in vascular inflammation and atherosclerosis.
Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women
Velpen, V. van der; Geelen, A. ; Hollman, P.C.H. ; Schouten, E.G. ; Veer, P. van 't; Afman, L.A. - \ 2014
American Journal of Clinical Nutrition 100 (2014)5. - ISSN 0002-9165 - p. 1269 - 1277.
in-vivo - glucose-metabolism - lipid-metabolism - soy isoflavones - phytoestrogens - profiles - protein - macrophage - insights - genotype
Background: Isoflavone supplements, consumed by women experiencing menopausal symptoms, are suggested to have positive effects on menopause-related adiposity and cardiovascular disease risk profile, but discussions about their safety are still ongoing. Objective: The objective was to study the effects of an 8-wk consumption of 2 different isoflavone supplements compared with placebo on whole-genome gene expression in the adipose tissue of postmenopausal women. Design: This double-blind, randomized, placebo-controlled crossover intervention consisted of 2 substudies, one with a low-genistein (LG) supplement (56% daidzein + daidzin, 16% genistein + genistin, and 28% glycitein + glycitin) and the other with a high-genistein (HG) supplement (49% daidzein + daidzin, 41% genistein + genistin, and 10% glycitein + glycitin). Both supplements provided ~100 mg isoflavones/d (aglycone equivalents). After the 8-wk isoflavone and placebo period, whole-genome arrays were performed in subcutaneous adipose tissue of postmenopausal women (n = 26 after LG, n = 31 after HG). Participants were randomized by equol-producing phenotype, and data analysis was performed per substudy for equol producers and nonproducers separately. Results: Gene set enrichment analysis showed downregulation of expression of energy metabolism–related genes after LG supplementation (n = 24) in both equol-producing phenotypes and oppositely regulated expression for equol producers (down) and nonproducers (up) after HG supplementation (n = 31). Expression of inflammation-related genes was upregulated in equol producers but downregulated in nonproducers, independent of supplement type. Only 4.4–7.0% of the genes with significantly changed expression were estrogen responsive. Body weight, adipocyte size, and plasma lipid profile were not affected by isoflavone supplementation. Conclusions: Effects of isoflavones on adipose tissue gene expression were influenced by supplement composition and equol-producing phenotype, whereas estrogen-responsive effects were lacking. LG isoflavone supplementation resulted in a caloric restriction–like gene expression profile for both producer phenotypes and pointed toward a potential beneficial effect, whereas both supplements induced anti-inflammatory gene expression in equol producers.
Phellinus linteus polysaccharide extracts increase the mitochondrial membrane potential and cause apoptotic death of THP-1 monocytes
Griensven, L.J.L.D. van; Verhoeven, H.A. - \ 2013
Chinese Medicine 8 (2013). - ISSN 1749-8546 - 13 p.
trail-induced apoptosis - cell-death - prostate-cancer - beta-glucans - tumor-growth - macrophage - necrosis - protein - fungi - differentiation
Background: The differentiation resp. death of human monocytic THP-1 cells induced by polysaccharide extracts of the medicinal mushrooms Phellinus linteus, Agaricus bisporus and Agaricus brasiliensis have been studied. This study aims to identify leads for the causal effects of these mushroom components on cell differentiation and death. Methods: THP-1 cells were treated with different polysaccharide extracts of mushrooms and controls. Morphological effects were observed by light microscopy. Flow cytometry was applied to follow the cell differentiation by cell cycle shifts after staining with propidium iodide, changes of mitochondrial membrane potential after incubation with JC-1, and occurrence of intracellular reactive oxygen species after incubation with hydroethidine. Principal component analysis of the data was performed to evaluate the cellular effects of the different treatments. Results: P. linteus polysaccharide extracts induced dose-dependent apoptosis of THP-1 cells within 24 h, while A. bisporus and A. brasiliensis polysaccharide extracts caused differentiation into macrophages. A pure P. linteus polysaccharide had no effect. Apoptosis was inhibited by preincubating THP-1 cells with human serum. The principal component analysis revealed that P. linteus, A. bisporus and A. brasiliensis polysaccharide extracts increased reactive oxygen species production. Both A. bisporus and A. brasiliensis polysaccharide extracts decreased the mitochondrial membrane potential, while this was increased by P. linteus polysaccharide extracts. Conclusions: P. linteus polysaccharide extracts caused apoptosis of THP-1 monocytes while A. bisporus and A. brasiliensis polysaccharide extracts caused these cells to differentiate into macrophages. The protective effects of human serum suggested that P. linteus polysaccharide extract induced apoptosis by extrinsic pathway, i.e. by binding to the TRAIL receptor. The mitochondrial membrane potential together with reactive oxygen species seems to play an important role in cell differentiation and cell death.
Host response to simultaneous infections with Eimeria acervulina, maxima and tenella: A cumulation of single responses
Cornelissen, J.B.W.J. ; Swinkels, W.J.C. ; Boersma, W.A. ; Rebel, J.M.J. - \ 2009
Veterinary Parasitology 162 (2009)1-2. - ISSN 0304-4017 - p. 58 - 66.
gamma-interferon production - lymphocyte subpopulations - immune-responses - gene-expression - coccidiosis - chickens - cytokine - quantification - susceptibility - macrophage
It is well known that broilers may be infected by different Eimeria strains at the same time and that different species infect specific parts of the gut. Cell mediated responses play a major role in the immune response in broilers after infection with Eimeria species. The cell mediated responses could be intestinal site specific and if this site specific cell mediated responses differ when other parts of the intestine are infected is unknown. To investigate this in the Eimeria infection model we analyzed the cell mediated responses to an infection with a single Eimeria species and with a mixture of different species of Eimeria such as E. acervulina, E. maxima or E. tenella in the duodenum, jejunum and caecum. The immune parameters we measured were intestinal T-cell and macrophage population dynamics as well as local cytokine mRNA expression. These parameters were related to the amount of Eimeria DNA that was measured in the intestine with an Eimeria strain specific quantitative PCR. The results showed that the strongest immune response was induced in the specific part of the intestine that was affected by each Eimeria strain. An E. acervulina infection mainly induced a duodenal CD8(+) T-cell and macrophage response as well as an increased IL-2, IL-4, IL-8, IL-10, and INF-gamma response. An E. maxima infection mainly induced a CD4(+) T-cell and macrophage response but also an increased IL-4, IL-8, and very strong INF-gamma (300-fold) expression in duodenum and jejunum. E. tenella induced a CD4(+) T-cell, macrophage response and an increase in the IL-2, IL-4, IL-8, IL-10, IL-18 and INF-gamma response in the caecum. The infection with a mixture of Eimeria species resulted in responses per intestinal segment that were similar to that observed following the single species infection. No synergistic or competitive effects were thus observed following a primary infection with a mixture of Eimeria species. In contrast, we observed an accumulation of the local effects of the single infections.
Gene expression responses to a Salmonella infection in the chicken intestine differ between lines
Hemert, S. van; Hoekman, A.J.W. ; Smits, M.A. ; Rebel, J.M.J. - \ 2006
Veterinary Immunology and Immunopathology 114 (2006)1. - ISSN 0165-2427 - p. 247 - 258.
messenger-rna expression - natural-resistance - immune-response - host responses - broiler lines - enteritidis - poultry - macrophage - mice - polymorphisms
Poultry products are an important source of Salmonella enterica. An effective way to reduce food poisoning due to Salmonella would be to breed chickens more resistant to Salmonella. Unfortunately host responses to Salmonella are complex with many factors involved. To learn more about responses to Salmonella in young chickens, a cDNA microarray analysis was performed to compare gene expression profiles between two chicken lines under control and Salmonella infected conditions. Newly hatched chickens were orally infected with S. enterica serovar Enteritidis. Since the intestine is the first barrier the bacteria encounter after oral inoculation, intestinal gene expression was investigated at different timepoints. Differences in gene expression between the two chicken lines were found in control as well as Salmonella infected conditions. In response to the Salmonella infection a fast growing chicken broiler line induced genes that affect T-cell activation, whereas in a slow growing broiler line genes involved in macrophage activation seemed to be more affected at day I post-infection. At days 7 and 9 most gene expression differences between the two chicken lines were identified under control conditions, indicating a difference in the intestinal development between the two chicken lines which might be linked to the difference in Salmonella susceptibility. The findings in this study have lead to the identification of novel genes and possible cellular pathways, which are host dependent. (c) 2006 Elsevier B.V. All rights reserved.
Immunomodulation by probiotic lactobacilli in layer and meat-type chickens
Koenen, M.E. ; Kramer, J. ; Hulst-van Arkel, M.C. van der; Heres, L. ; Jeurissen, S.H.M. ; Boersma, W.J.A. - \ 2004
British Poultry Science 45 (2004). - ISSN 0007-1668 - p. 355 - 366.
increased body-weight - salmonella-enteritidis - monoclonal-antibodies - competitive-exclusion - bacteria - mice - resistance - macrophage - responses - growth
1. The aim of the experiments was to evaluate whether selected probiotic lactobacillus strains have different immunomodulating effects in layer- and meat-type strain chickens. 2. Humoral and cellular specific and non-specific immune responses were studied by experiments on cellular proliferation, entry and survival of Salmonella bacteria in gut and spleen leukocytes, immunoglobulin isotypes and specific immunoglobulin titres. 3. The effects of two different feeding regimes (short and continuous feeding) and doses for administration of lactobacilli were studied. 4. The lactobacillus strains that were evaluated showed modulating effects on the immune system of layer- and meat-type chickens. 5. In meat-type strain chickens the lactobacilli had a stimulating effect when the chickens were young (up to 3 weeks) and the dose was relatively high, whereas in layer- type chickens a lower effective dose and discontinuous administration was also effective. 6. Immunoprobiotic lactobacilli can have a positive effect on humoral and cellular immune responses in layer- and meat-type strain chickens, but the lactobacillus strain to be used, the age of the animals and effective dose of lactobacilli to be administered need to be optimised.