Interactions between adipose tissue and the immune system in health and malnutrition

Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological conditions.     

Regulatory interplay of RpoS and RssB controls motility and colonization in Vibrio cholerae

Cholera is a life-threatening diarrheal disease caused by the human pathogenic bacterium Vibrio cholerae. Regulatory elements are essential for bacterial transition between the natural aquatic environment and the human host. One of them is the alternative sigma factor RpoS and its anti-sigma factor RssB. Regulation principles seem to be conserved among RpoS/RssB interaction modes between V. cholerae and Enterobacteriaceae species, however the associated input and output pathways seem different. In Escherichia coli, RpoS/RssB is important for the activation of an emergency program to increase persistence and survival. Whereas, it activates motility and chemotaxis in V. cholerae, used strategically to escape from starvation conditions. We characterised a starvation-induced interaction model showing a negative feedback loop between RpoS and RssB expression. We showed by genotypic and phenotypic analysis that rssB influences motility, growth behaviour, colonization fitness, and post-infectious survival. Furthermore, we found that RssB itself is a substrate for proteolysis and a critical Asp mutation was identified and characterised to influence rssB phenotypes and their interaction with RpoS. In summary, we present novel information about the regulatory interaction between RpoS and RssB being active under in vivo colonization conditions and mark an extension to the feedback regulation circuit, showing that RssB is a substrate for proteolysis.     

Experimental study of non-alcoholic fatty liver disease (NAFLD) on a model of starving chickens: is generalization of steatosis accompanied by fibrosis of the liver tissue?

The objective of this work was to study the mechanism of liver parenchyma development under the influence of restriction of diet. Useful information is presented about the pathologic features associated with diet restriction in a chicken animal model of NAFLD. There were 96 chickens of two genotypes, Ross 308 and Cobb 500, in the experiment. The control group was fed a standard mixture ad libitum (ADL). The first experimental group, under restriction from the age of 2 weeks, was fed 80% ADL. The second experimental group was fed 65% ADL from the age of 2 weeks. There were 16 animals in each group. The experiment lasted 5 weeks. Liver parenchyma samples were obtained at the age of 35 days by the necropsy method and then processed by standard histologic methods. The slices were stained by standard staining: hematoxylin-eosin and by Sirius red kit for collagen type I and reticulin visualization. Hepatocyte diameter and the proportion of interstitial tissue to the parenchyma of the liver were measured objectively. Microvesicular liver steatosis was observed after 35 days of restriction. Hepatocyte diameter was significantly influenced by sex, genotype, and the experimental group. The proportion of interstitial tissue to the liver parenchyma was highly influenced by genotype and group, but there were no interactions. An increase in the steatosis histologic grade is associated with inflammatory changes, with decrease of hepatocyte diameter and with a decreasing proportion of interstitial tissue to the liver parenchyma. The results show that early restriction is not associated with the development of fibrosis of the liver tissue.     

Effect of poly‐3‐hydroxybutyrate synthase mutation on the metabolism of Ensifer (formerly Sinorhizobium) meliloti

In order to investigate the effect of poly‐3‐hydroxybutyrate synthase mutation (phbC) on the synthesis of exopolysaccharides (EPS) and glycogen, on the symbiotic properties and on the survival under specific conditions of Ensifer meliloti (formerly Sinorhizobium), a new stable phbC mutant of Ensifer meliloti 41 was isolated and characterized. Under poly‐3‐hydroxybutyrate accumulation conditions, the phbC ‐minus mutant (strain 41003) accumulates more glycogen and less exopolysaccharides as compared to the wild‐type strain, and grows poorly in pyruvate as carbon source. The inactivation of aniA, encoding for a global carbon flux regulator, restores in E. meliloti 41003 the ability to grow on pyruvate, indicating a new role for this gene. Survival studies of E. meliloti 41 and 41003 under carbon free medium in both liquid and soil microcosms showed prolonged survival of E. meliloti 41 under these adverse conditions as compared to the mutant strain unable to accumulate the polyester. On the other hand, the accumulation of P(3HB) gave no significant advantage in survival under oxygen‐limiting conditions. In both strains, E. meliloti 41 and 41003, nodule‐inducing ability on alfalfa plants and acetylene reduction activity did not significantly differ from each other, although the mutant strain was less competitive in terms of root colonization. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Hexose metabolism in pancreatic islets

Islets from fed and 3-day-starved rats were incubated for 60 min in the presence of either 2.8 or 16.7 mM d-glucose, mixed with tracer amounts ofd-[5-³H]glucose,d-[3,4-¹⁴C]glucose,d-[6-¹⁴C]glucose andd-[2-¹⁴C]glucose. Starvation decreased the generation of³HOH fromd-[5-³H]glucose and the production of¹⁴CO₂ from¹⁴C-labelledd-glucose, both at low and high hexose concentrations. In islets from starved and fed rats, a rise ind-glucose concentration preferentially stimulated oxidative glycolysis, pyruvate decarboxylation and acetyl residue oxidation, relative tod-glucose utilization. At both low and high hexose concentrations and in both fed and starved rats, the decarboxylation of pyruvate exceeded the oxidation of glucose-derived acetyl residues, the C₁ of such residues being more efficiently converted to¹⁴CO₂ than their C₂. Starvation decreased oxidative glycolysis more severely than non-oxidative glycolysis, impaired the preferential stimulation ofd-[3,4-¹⁴C]glucose oxidation relative tod-[5-³H]glucose utilization as observed in response to a rise in hexose concentration, and lowered the ratio betweend-[6-¹⁴C]glucose oxidation and hexose utilization. It is proposed, therefore, that the short-term regulation of mitochondrial oxidative events byd-glucose is itself modulated in islet cells by the nutritional status.     

谷氨酰胺对饥饿大鼠内毒素移位和肠黏膜免疫功能的影响

目的：探讨饥饿后大鼠肠黏膜形态学结构的变化规律,并动态观察GLN肠内补充对饥饿大鼠内毒素移位和肠黏膜免疫功能的影响.方法：采用饥饿大鼠模型,将90只3月龄♂SD大鼠随机分为正常对照组N：(给予正常饮食n =10)、饥饿组A(n=40)、谷氨酰胺组B(n= 40)3个大组,分别于饥饿后3,5,7,9d,取门静脉血测血浆内毒素的变化,在光镜下观察肠组织的组织形态学改变,利用免疫组化技术检测肠黏膜组织中SIgA的表达和CD4~ 、CD8~ T细胞的数量.结果：A组大鼠饥饿后,3d可见小肠黏膜明显萎缩,绒毛变短、变稀.部分黏膜上皮细胞变性、坏死、脱落,绒毛横径增宽,高度缩短；至饥饿后9d上述变化更加明显.B组在饥饿后3d较同时间点A组肠黏膜损伤有明显的改善,小肠的黏膜厚度、绒毛数量、高度增加,至饥饿后5d基本恢复至N组水平.随着饥饿时间的延长小肠黏膜再次出现黏膜萎缩、绒毛变短、变稀,黏膜上皮细胞变性、坏死、脱落.但明显轻于同时间点的A组.饥饿后各时间点血浆内毒素与N组相比明显升高,A,B组均在饥饿后7d达到高峰,B组在饥饿后3,5,7,9d较A组降低且有非常显著性差异(322.4±65.1,389.4±32.6,464.4±76.6,413.7±67.2EU/L vs 527.1±74.9,546.3±65.7,623.9±85.9,587.5±140.8EU/L,均P＜0.01).与N组比较,A组大鼠肠黏膜SIgA及CD4~ ,CD8~ T细胞数量明显减少,差异有显著性性(P＜0.05,P＜0.01).补充GLN后,SIgA及CD4~ ,CD8~ T细胞数量明显升高,B组与A组比较差异非常显著(P＜0.01).结论：大鼠饥饿后早期确有肠黏膜组织结构受损,发生内毒素移位,同时伴有肠黏膜免疫学屏障受损.早期给予GLN可减轻肠黏膜的受损,明显降低内毒素移位,增强肠黏膜的免疫功能发挥肠黏膜的保护作用.     

Ceroid/lipofuscin-loaded human fibroblasts show decreased survival time and diminished autophagocytosis during amino acid starvation

To test whether heavy accumulation of ceroid/lipofuscin can disturb important functions of the lysosomal system, AG-1518 human fibroblasts, ceroid/lipofuscin-loaded (following prolonged culture at normobaric hyperoxia) or not, were exposed to amino acid starvation. Ceroid/lipofuscin-loading resulted in decreased cellular survival. Also, there was an inverse relationship between amounts of ceroid/lipofuscin and the survival time of individual cells within the same cultures. Ceroid/lipofuscin-loaded fibroblasts displayed diminished autophagocytotic capacity, as demonstrated by electron microscopy and by treatment of cell cultures with NH₄Cl (which inhibits autophagocytotic degradation by increasing intralysosomal pH) for 1 week before ensuing starvation. The latter treatment increased survival of control cells (due to deposition of nondegraded autophagocytosed material before start of starvation), but not that of ceroid/lipofuscin-loaded cells. Moreover, when NH₄Cl treatment was combined with starvation, both groups of cells showed approximately the same shortened survival times, testifying to the causal relationship between diminished autophagocytosis and decreased survival of starving ceroid/lipofuscin-loaded cells. We hypothesize that large amounts of undegradable ceroid/lipofuscin within the acidic vacuolar compartment may interfere with lysosomal function, resulting in poor renewal of long-lived proteins and worn-out/damaged organelles, decreased adaptability, and cell death.     

Mineral metabolism during short-term starvation in man

Plasma and urine electrolytes were measured in five healthy non-obese young adults before, during and after a four-day period of total starvation (distilled water only). Plasma sodium, chloride and bicarbonate concentrations decreased in all subjects by a mean value of 4 mmol/l, whereas the sum of acetoacetate and hydroxybutyrate concentrations increased by 4-6 mmol/l. These changes occurred without alterations in the state of hydration or vascular volume. Hydroxybutyrate and ammonium ions became the main urinary ions during starvation, whereas sodium and chloride, which were quantitatively the most important urinary electrolytes before starvation, decreased four-fold, and potassium two-fold. Plasma zinc concentrations rapidly increased in all subjects by a mean of 4 mumol/1 (25%) and returned to normal on refeeding. The excretion of zinc in urine trebled and continued to rise on refeeding. There were no major changes in the excretion of calcium, magnesium, phosphate or sulphate during the starvation period. From knowledge of the intracellular concentrations of various minerals and extent of breakdown of lean tissues (N excretion), it is suggested that most of the urinary calcium, magnesium and phosphate probably originates from bone, and that the amount of zinc in urine is only a small fraction of that which is likely to be released from the breakdown of lean tissues. It is also suggested that the continued excretion of zinc on refeeding is due to release of zinc from tissues which 'buffered' it during the starvation period. This study provides useful data in non-obese individuals with which to compare changes which occur in post-traumatic and post-infective starvation.     

La famine à l’hôpital psychiatrique de Cadillac durant la Seconde Guerre mondiale : l’envers du décor

During the Second World War, the behavior of some staff members of French psychiatric hospitals was not always honest, exemplary or free of reproach. The theft of food for the mentally ill people sometimes worsened the famine and excess mortality of these patients. Using original research material from the Departmental Archives of the Gironde, the author discusses various historical documents proving that during this period of war several employees at the psychiatric hospital in Cadillac received administrative or judicial sanctions for fraudulently diverting the food ant property of patients to their detriment. This is the first French study to focus on this issue.     

Comment gérer la progression calorique lors de la renutrition

Total or partial starvation decrease both body fat mass and lean body mass. The latter comes along with a spectacular drop in intracellular glycogen and nucleotides phosphate, associated with decreased intracellular fluid volume and total body potassium, magnesium and phosphate pools. Upon renutrition, the provision of carbohydrate and the ensuing hyperinsulinemia cause a swift reversal of cellular hypometabolism, and to a rapid transport of extracellular phosphate, potassium and magnesium into the cells. This is more specifically related administration of carbohydrate and a rapid rise in plasma insulin concentration, which is responsible for an immediate increase in cellular energy metabolism, inhibition of lipid oxidation and stimulation of glycogen synthesis. These phenomenons can be some times at the origin of set of acute hydro-electrolytic imbalances and cardiac and neural dysfunctions known as “the refeeding syndrome”. Occurrence of this syndrome can be largely prevented by a slow, graded administration of energy and carbohydrate upon initiation of refeeding and by the systematic administration of potassium supplement. The initial phase of refeeding also requires a careful monitoring of blood phosphate and magnesium concentrations, with administration of exogenous supplements when required.