Phosphatidylserine, another player in macrophage recruitment in white adipose tissue?

Macrophage infiltration in white adipose tissue (WAT) underlies the development of the obesity-associated chronic inflammatory state. In this article current knowledge is reviewed with respect to adipocyte-driven mechanisms responsible for macrophage recruitment and activation in WAT. Adipocyte hypertrophy, adipocyte hypoxia, altered adipokine profiles under stress conditions and adipocyte death is discussed. In addition, new data is provided that shows phosphatidylserine exposure in human adipocytes under hypoxic conditions. This may represent an additional mechanism that plays a role in macrophage recruitment in WAT.Adipobiology 2010; 2: 23-32

The role of proteomics research in discovering adipocyte-secreted proteins and their (patho)physiological role

Intercellular communication plays an essential role in the (patho)physiological function of the adipose tissue. (Pre)adipocyte-secreted proteins, collectively known as adipokines, serve as signaling molecules in a paracrine and endocrine fashion. Adipokine profiles are dynamic and can change dramatically leading to metabolic complications during obesity or can return towards a more beneficial profile under influence of weight loss interventions. Here it is reviewed how proteomics technologies contributed to identify (pre)adipocyte-secreted proteins. Different secretion routes are highlighted with a particular focus on microvesicle-mediated secretion. Furthermore, novel information is provided on identification of human adipokines and on the application of proteomics technologies to discover unknown adipokine-receptor interactions.Adipobiology 2012; 4: 33-40

Novel adipocyte features discovered by adipoproteomics

Obesity and its associated complications will be the most important near-future medical burden in Western-type societies. One hallmark of obesity is the differentiation of preadipocytes into mature fat-loaded adipocytes present in subcutaneous and visceral fat depots. Furthermore, (pre)adipocytes secrete proteins, known as adipokines, with changing profiles during fat accumulation. Adipocytes serve in important function with respect to energy homeostasis, body insulation and organ protection. Adipocyte dysfunction results in the initiation and progression of obesity-associated disorders. Obviously, knowledge of the adipocyte behavior under different nutritional conditions and the cross-talk of adipocytes with other cells and organs are key issues to develop proper intervention strategies. A full understanding of the adipocyte behavior requires a systems biology approach with integrated transcriptomics, proteomics and metabolomics data. This review focuses on the contribution of proteomics research in adipocyte biology. Proteome studies on adipocytes exist for almost 30 years but are boosted in the last decade with the enormous technological developments in mass spectrometry technology. The relevance of proteomics technologies in understanding molecular aspects of adipocyte biology is discussed. Recent novel findings and particularly the identification of novel adipokines are highlighted.Adipobiology 2009; 1: 7-18

Mechanistic Analysis of Fat Loss and Regain by Using an in Vitro Human Adipocyte Model System

The prevalence of overweight and obesity has risen in recent years, causing a global public health problem due to an increased risk for the development of cardiometabolic diseases (atherosclerosis, hypertension, type 2 diabetes mellitus, metabolic syndrome) and cancers (1). The white adipose tissue (WAT) is a major player in the link between overweight and health complications. One factor is the fat storage capacity of the WAT because lipid overload leads to ectopic lipid accumulation in other peripheral tissues like skeletal muscle (2) and liver (3). This often leads to insulin resistance (4). Another role of the WAT in the link between overweight and health complications lies in the secretion by the adipocytes of over 600 peptide hormones, referred to as adipokines (5), which regulate whole body metabolism (5, 6). When people become obese, the profile of secreted peptide hormones changes as for instance is obvious from a decrease in the plasma level of adiponectin, a multifunctional adipokine that increases glucose uptake by skeletal muscle

Starvation Induces Phase-Specific Changes in the Proteome of Mouse Small Intestine

Food deprivation results in metabolic, structural, and functional changes in the small intestine that influences gut mucosal integrity, epithelial cell proliferation, mucin synthesis, and other processes. The underlying mechanisms are still unclear, which lead to the study of molecular effects of short-term and long-term starvation in the intestine of mice. A comparative proteomics approach, combining two-dimensional gel electrophoresis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, was used to identify intestinal proteins whose expression is changed under different starvation conditions (0, 12, 24, and 72 h). In total, the expression levels of 80 protein spots changed significantly between the different groups. The results demonstrate that after 12 h of starvation, mainly proteins involved in glycolysis and energy metabolism show decreased expression levels. Starvation for 24 h results in a down-regulation of proteins involved in protein synthesis and amino acid metabolism. Simultaneously, proteins with a protective role, e.g., reg I and II, glutathione peroxidase 3, and carbonic anhydrase 3, are clearly up-regulated. The last starvation phase (72 h) is characterized by increased ezrin expression, which may enhance villus morphogenesis critical for survival. Together, these results provide novel insights in the intestinal starvation response and may contribute to improved nutritional support during conditions characterized by malnutrition

Weight loss-induced stress in subcutaneous adipose tissue is related to weight regain

Initial successful weight loss is often followed by weight regain after the dietary intervention. Compared with lean people, cellular stress in adipose tissue is increased in obese subjects. However, the relation between cellular stress and the risk for weight regain after weight loss is unclear. Therefore, we determined the expression levels of stress proteins during weight loss and weight maintenance in relation to weight regain. In vivo findings were compared with results from in vitro cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. In total, eighteen healthy subjects underwent an 8-week diet programme with a 10-month follow-up. Participants were categorised as weight maintainers or weight regainers (WR) depending on their weight changes during the intervention. Abdominal subcutaneous adipose tissue biopsies were obtained before and after the diet and after the follow-up. In vitro differentiated SGBS adipocytes were starved for 96 h with low (0.55 mm) glucose. Levels of stress proteins were determined by Western blotting. WR showed increased expressions of beta-actin, calnexin, heat shock protein (HSP) 27, HSP60 and HSP70. Changes of beta-actin, HSP27 and HSP70 are linked to HSP60, a proposed key factor in weight regain after weight loss. SGBS adipocytes showed increased levels of beta-actin and HSP60 after 96 h of glucose restriction. The increased level of cellular stress proteins in the adipose tissue of WR probably resides in the adipocytes as shown by in vitro experiments. Cellular stress accumulated in adipose tissue during weight loss may be a risk factor for weight regain

Bedömning av status för nationellt förvaltade fisk- och skaldjursbestånd

Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) presenterar årligen statusbedömningar för nationellt förvaltade fisk- och skaldjursbestånd i svenska vatten på webbportalen www.fiskbarometern.se. Fiskbarometerns statusbedömningar av fisk- och skaldjursbestånd, utgör ett viktigt underlag för hållbart nyttjande, bevarandeåtgärder och uppföljning inom fisk-, vatten- och miljöförvaltningen. I denna rapport redovisas metodiken för dessa statusbedömningar. Metodiken bidrar till en standardiserad och kvalitetssäkrad bedömningsprocess som är transparent och som vilar på vetenskaplig grund. För de flesta bestånd i Fiskbarometern baseras bedömningen på indikatorer indelade i dödlighet, biomassa/abundans och storleks-/åldersstruktur, vilka motsvarar Havsmiljödirektivets tre kriterier för bedömning av kommersiellt nyttjade bestånd (2008/56/EC). Baserat på sammanvägningen av de tre kriterierna ges respektive bestånd sedan en av fem möjliga statusbedömningar:• kan ej bedömas • mycket sannolikt inte inom biologiskt säkra gränser • sannolikt inte inom biologiskt säkra gränser • sannolikt inom biologiskt säkra gränser • mycket sannolikt inom biologiskt säkra gränserFör några nationellt förvaltade bestånd finns eller pågår arbete med att utveckla analytiska beståndsmodeller. I den här rapporten presenteras riktlinjer för kvalitetssäkring och tillämpning av dem översiktligt, men den vetenskapliga granskningen av sådana modeller hanteras separat inom en process som kallas riktmärkning, vilken inte beskrivs i denna rapport. Utfall från dessa modeller översätts till samma statuskategorier som för de indikatorbaserade bedömningarna

Reorganization of the nuclear lamina and cytoskeleton in adipogenesis

A thorough understanding of fat cell biology is necessary to counter the epidemic of obesity. Although molecular pathways governing adipogenesis are well delineated, the structure of the nuclear lamina and nuclear-cytoskeleton junction in this process are not. The identification of the ‘linker of nucleus and cytoskeleton’ (LINC) complex made us consider a role for the nuclear lamina in adipose conversion. We herein focused on the structure of the nuclear lamina and its coupling to the vimentin network, which forms a cage-like structure surrounding individual lipid droplets in mature adipocytes. Analysis of a mouse and human model system for fat cell differentiation showed fragmentation of the nuclear lamina and subsequent loss of lamins A, C, B1 and emerin at the nuclear rim, which coincides with reorganization of the nesprin-3/plectin/vimentin complex into a network lining lipid droplets. Upon 18 days of fat cell differentiation, the fraction of adipocytes expressing lamins A, C and B1 at the nuclear rim increased, though overall lamin A/C protein levels were low. Lamin B2 remained at the nuclear rim throughout fat cell differentiation. Light and electron microscopy of a subcutaneous adipose tissue specimen showed striking indentations of the nucleus by lipid droplets, suggestive for an increased plasticity of the nucleus due to profound reorganization of the cellular infrastructure. This dynamic reorganization of the nuclear lamina in adipogenesis is an important finding that may open up new venues for research in and treatment of obesity and nuclear lamina-associated lipodystrophy

Glutamine regulates the expression of proteins with a potential health-promoting effect in human intestinal Caco-2 cells

Glutamine is an essential amino acid for the enterocytes with respect to maintaining the gut mucosal integrity and function. This study was conducted to explore a molecular basis for the beneficial effects of glutamine on intestinal cells by searching for glutamine-dependent changes in the proteome. Caco-2 cells were exposed to different concentrations of L-glutamine with or without L-methionine sulfoximine, an inhibitor of the glutamine synthetase activity. 2-DE combined with MALDI-TOF-MS was used to identify proteins whose expression is changed by glutamine. To assess the relative protein synthesis rate, incorporation of L-[2H5]glutamine into individual proteins was monitored. The expression levels of 14 proteins changed significantly with the glutamine availability. Examples of differentially expressed proteins with potential health-promoting effects on the intestine are plasma retinol-binding protein, ornithine aminotransferase, apolipoprotein A-I, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, and acyl-CoA synthetase 5. Expression of these proteins was not changed by arginine deprivation. The differential change in the expression levels of the proteins was not correlated with their rate of synthesis, excluding an effect of glutamine depletion on general protein synthesis. Together, this study shows a gene-specific effect of glutamine on intestinal cell