Microglial cells from psychologically stressed mice as an accelerator of cerebral cryptococcosis

Severe stress decreases the resistance of hosts exposed to microbial infections. As compared with two groups of control mice (normal mice, food-and-water-deprived mice [FWD mice]), restraint-stressed mice (RST mice) were shown to be greatly susceptible to intracerebral growth of Cryptococcus neoformans. The susceptibility of FWD mice to cerebral cryptococcosis increased to the level shown in RST mice, when these groups of mice were inoculated with microglial cells from the brains of RST mice. However, the susceptibility of FWD mice to cerebral cryptococcosis was not influenced by the adoptive transfer of microglial cells from normal mice or FWD mice. Microglial cells from RST mice produced CC-chemokine ligand-2 (CCL-2/monocyte chemoattractant protein 1), but not microglial cells from FWD mice. The resistance of RST mice to cerebral cryptococcosis was improved to the extent shown in FWD mice, when they were treated with anti-CCL-2 antibody. However, the susceptibility of normal mice and FWD mice to cerebral cryptococcosis increased to that shown in RST mice, when they were treated with rCCL-2. Microglial cells from RST mice were discriminated from the same cell preparations derived from FWD mice by their abilities to produce CCL-2, to phagocytize C. neoformans cells and to express Toll-like receptor 2. These results indicate that the resistance of RST mice to cerebral cryptococcosis is diminished by CCL-2 produced by microglial cells that are influenced by restraint stress.     

Resistance to tolerance induction in B cells of autoimmune mice—Abnormal expansion of low affinity IgG-producing B-cell population

Several strains of mice are known to develop spontaneous autoimmune diseases like lupus erythematosus and they show various immunological abnormalities as well. Despite different genetic backgrounds, they manifest various immunological abnormalities in common, e.g., polyclonal B-cell activation (PBA) and resistance to tolerance induction. To elucidate mechanisms of the development of autoimmunity, tolerance inducibility was examined in autoimmune and normal mice using trinitrophenylated carboxymethyl cellulose (TNP-CMC) as tolerogen which is known to induce TNP-specific B-cell tolerance without the participation of T cells. NZB and MRL/Mp-lpr/lpr mice were used as autoimmune mice and C57BL/6, BALB/c, and MRL/Mp-+/+ mice as nonautoimmune mice. When TNP-CMC-injected mice were challenged with T-independent antigens, all of the mice tested were shown to be tolerant. In contrast, when TNP-CMC-injected mice were challenged with T-dependent antigen and secondary IgG responses were assessed, autoimmune mice showed rather hyperreactivity, while nonautoimmune mice showed hyporesponsiveness. Cyclophosphamide improved this defective tolerance inducibility. By the solid-phase radioimmunoassay it was revealed that average affinity of serum anti-TNP antibodies produced in TNP-CMC-injected mice was low. Such low affinity antibodies were produced in large amount in autoimmune mice. Hence, it was suggested that B-cell clones destined to produce low affinity IgG antibodies were responsible for the resistance to tolerance induction and such clones were expanding in autoimmune mice.     

肥胖患者HFA小鼠模型的建立

目的研究肥胖患者的肠道菌群在无菌小鼠体内的定植规律。方法选取20只无菌KM小鼠,接种肥胖患者的粪便,构建菌群人源化(HFA)动物模型,利用变性梯度凝胶电泳技术(DGGE)评价患者肠道菌群在无菌小鼠体内的定植规律。结果 HFA小鼠菌群平均丰富度(richness,S)为12.04±3.68,肥胖患者的条带S为24,为HFA小鼠S的2倍;肥胖患者Shannon指数(H')为3.02,HFA小鼠平均H'为2.46±0.33;HFA小鼠与人肠道菌群的总相似度为26%;大部分雌性HFA小鼠与雄性HFA小鼠在聚类分析图上分离,且雄性HFA小鼠与患者更为相似。结论HFA小鼠体内能部分模拟肥胖患者的微生物区系,且与患者性别相同的小鼠模拟得更好。本实验建立的HFA模型为肥胖与肠道菌群关系的进一步研究提供新的选择。     

Duration and patterns of transmission of Theiler's mouse encephalomyelitis virus infection

The duration and patterns of Theiler's murine encephalomyelitis virus (TMEV) transmission were studied in eight index mice inoculated orally. Transmission was monitored by testing for seroconversion to TMEV in sentinel mice in direct contact with index mice and in other sentinel mice in contact with bedding soiled by index mice. For the first 14 weeks after inoculation, two contact sentinels were housed with each index mouse for 1 week, then replaced with two new sentinels. For the remaining 16 weeks, contact sentinels were changed monthly. All index mice transmitted TMEV continuously (weekly) for 4 to 9 weeks. Thereafter, six index mice transmitted virus intermittently. All index mice ceased transmitting TMEV 7 to 22 weeks post-inoculation. Results obtained from sentinel mice in contact with bedding soiled by index mice were 86% concordant with those using contact sentinel mice. Seven index mice were treated with cyclophosphamide or hydrocortisone 30 weeks post-inoculation. One cyclophosphamide treated mouse reinitiated virus shedding.     

Isolation effect in mice (Mus musculus): (i) Does it really induce aggression?

In previous studies, isolated mice are found to be extremely more aggressive than group-reared mice. In most of those studies, however, the pairings of the group-reared mice were randomly determined, without attention to individuals' ranks in their home cages. In this study, the effect of isolation was analyzed by comparing isolated mice with dominants of group-reared mice. In experiment 1 the group-reared mice were randomly chosen as in previous studies. Isolated mice were significantly more aggressive, but the pairings of the group-reared mice were found to be all dominant vs. subordinate. In experiment 2, the group-reared dominants encountered unfamiliar dominants in an unfamiliar place. Dominant mice were found to be less aggressive than the isolated mice. This result was inconsistent with the “territorial dominant hypothesis” on the hyperaggressiveness of the isolated mice. Sequential analysis of behavior clarified that the isolated mice had a sequential pattern quite different from the group-reared mice, and provided an illustrative figure for the “escalation hypothesis”. The lack of aggression in the group-reared mice, however, left a question about the sequence similarity of aggressive behavior in isolaed and group-reared mice.     

Oocyst shedding by cats fed isolated bradyzoites and comparison of infectivity of bradyzoites of the VEG strain Toxoplasma gondii to cats and mice

Infectivity of bradyzoites of the VEG strain of Toxoplasma gondii was compared in cats and mice. For this, tissue cysts were separated from brains of infected mice using a Percoll gradient, and bradyzoites were released by incubation in acidic pepsin solution. After filtration through a 3-microm filter, bradyzoites were counted and diluted 10-fold in RPMI tissue culture medium. Dilutions estimated to have 1, 10, 100, and 1,000 bradyzoites were fed to cats and inoculated into mice, orally or subcutaneously (s.c.). Three experiments were performed. In experiment 1, 2 of 2 cats fed 1,000 bradyzoites, 1 of 2 cats fed 100 bradyzoites, 1 of 4 cats fed 10 bradyzoites, and 1 of 4 cats fed 1 bradyzoite shed millions of oocysts; 1,000 bradyzoites were infective to all 4 inoculated mice s.c. but not to 4 mice inoculated orally, and 100 bradyzoites were infective to 2 of 4 mice injected s.c. but not to 4 mice inoculated orally. All 16 mice (8 oral, 8 s.c.) injected with 1 or 10 bradyzoites were negative for T. gondii. In experiment 2, 1 of 4 cats fed 10 counted bradyzoites shed oocysts; the same inocula were not infective to 4 mice injected s.c. In experiment 3, 3 of 4 cats fed 1,000 bradyzoites shed oocysts and the inocula were infective to 10 of 10 mice s.c. and 4 of 10 mice orally; 4 of 4 cats fed 100 bradyzoites shed oocysts and the inocula were infective to 6 of 10 mice s.c. and 0 of 10 mice orally; 10 bradyzoites were not infective to cats and mice. Results indicate that bradyzoites are more infective to cats than to mice, and cats can shed millions of oocysts after ingesting just a few bradyzoites.     

Chronic stress reduces body fat content in both obesity-prone and obesity-resistant strains of mice

Unpredictable stressors have been used to assess the effect of stress on energy metabolism in obesity-prone (C57BL6J) and obesity-resistant (AJ) mice. Mice were exposed for 25 days to a stress protocol. Both strains of mice were divided into groups of control and stressed mice, which had access to either a high-fat or a high-carbohydrate diet. Twenty-four hours after the last session of stress, mice were sacrificed for blood and brain collections. Insulin, corticosterone, and glucose concentrations in plasma were measured, and expressions of corticotropin-releasing factor (CRF) in the paraventricular hypothalamic nucleus (PVH) and the central amygdala (CeA) were determined by in situ hybridization. Stressed mice in all groups had lower body fat contents than control mice, and all mice fed with the high-fat diet had heavier retroperitoneal and inguinal fat pads than mice fed with carbohydrate. CRF mRNA level in the CeA was lower in B6 mice than in AJ mice. Stressed mice had a lower expression of CRF in the CeA than control mice. In conclusion, chronic stress reduces body fat content in obesity-prone as well as in obesity-resistant mice.     

两种自发性2型糖尿病小鼠生物学特性比较

目的分别以C57BL/6JSlac和C57BL/KsJ-db/＋表型正常小鼠为对照组,比较自发性2型糖尿病KK-Ay/Ta和C57BL/KsJ-db/db小鼠的体生长曲线、糖代谢曲线、血清胰岛素水平、主要脏器重量、脏器系数等生物学特性的差异,并探讨其肾脏、肝脏和胰腺等组织病理学变化。方法在各自实验周期内,每2周测定实验组和对照组小鼠的体重、血糖以及血清胰岛素水平,实验结束后处死,脏器、脂肪称重,部分组织制作病理切片。结果 （1）KK小鼠体重远高于db/db小鼠,且同品系间雄性小鼠重于雌性小鼠（P〈0.05）;（2）同品系间雄性小鼠的血糖值明显大于雌性小鼠（P〈0.05）,db/db小鼠出现血糖异常症状比KK小鼠早,且血糖值大于KK小鼠（P〈0.05）,而KK小鼠血糖异常持续时间则较db/db小鼠长;（3）KK小鼠的血清胰岛素水平明显高于db/db小鼠（P〈0.05）,同品系雌雄小鼠间没有明显差异（P〉0.05）;（4）雄性KK小鼠脂肪系数及部分脏器萎缩程度大于雌性,而db/db小鼠雌雄间则无明显差异（P〉0.05）,同时db/db小鼠脾脏和胰腺的萎缩程度及脂肪系数大于KK小鼠（P〈0.05）,而KK小鼠肝脏的萎缩程度则大于db/db小鼠;（5）糖尿病模型小鼠肾脏、肝脏以及胰腺组织均出现明显病变。结论 KK-Ay/Ta和C57BL/KsJ-db/db小鼠均是肥胖的,伴有高血糖、高度胰岛素抵抗,肝脏、肾脏病变和胰岛功能不足的适用性2型糖尿病动物模型,且db/db小鼠血糖出现异常比KK小鼠早、脂肪系数大,而KK小鼠血糖异常持续时间较db/db小鼠长,同时血清胰岛素水平远大于db/db小鼠。     

Characteristic faecal flora of NC mice

The composition of faecal flora of NC mice was compared with that of CF #1 mice. NC- and CF #1-germfree (GF) mice were cage-mated with NC- or CF #1-conventional (CV) mice in an isolator. The faecal flora of these ex-GF mice was dependent on the recipient mouse strain modifying colonization by the donor mouse bacteria. Although NC- and CF #1-pups removed by hysterectomy were fostered to different strains, almost all these mice at 8 weeks old had a strain characteristic pattern of faecal flora regardless of the foster strains. In GF mice mono-associated with a Lactobacillus strain or a Bifidobacterium strain isolated from faeces of CV mice, the numbers of these bacteria in the stomach and small intestine of NC mice were lower than those of CF #1 mice. In GF mice associated with chloroform-treated faeces of CV mice, and a Lactobacillus strain or a Bifidobacterium strain, the numbers of these bacteria in the stomach and all parts of the intestine of NC mice were considerably lower than those of CF #1 mice. These results suggested that the composition of faecal flora of NC mice were characteristic, i.e. the fact that the numbers of lactobacilli were low compared with CF #1 mice with ordinary faecal flora and the colonization of bifidobacteria, peptococcaceae and eubacteria on ES agar in NC mice intestine differed, was due to genetic factors.     

Effects of some factors on the susceptibility of Peromyscus leucopus to infestation by larvae of cuterebra fontinella (Diptera: Cuterebridae).

Two levels of 3 factors, (1) host age, (2) host dietary state in regard to vitamin A, and (3) previous infestation history, were tested individually and in combinations for their effects on the susceptibility of Peromyscus leucopus to infestation by larvae of the rodent bot fly, Cuterebra fontinella. Previous infestation was the only significant single factor. Previously uninfested (Pu) mice usually were more susceptible to infestation than previously infested (Pi) mice. Interactions of age and state of vitamin A had the following effects: 1) Young Pu mice that had been denied vitamin A were much less susceptible to infestation than equivalent mice that had been fed diets containing the vitamin; and 2) when Pu mice were deficient in vitamin A, old mice were more susceptible than young mice but when Pu mice were not deficient in the vitamin, young mice were more susceptible. These findings may have significance for natural infestations of P. leucopus.     

皮下种植黑色素瘤对小鼠血液中脂肪和氨基酸代谢的影响*

目的:探讨皮下种植黑色素瘤对小鼠血液中相关脂肪和氨基酸代谢的影响。方法:野生型小鼠皮下种植B16黑色素瘤细胞,两周后观察小鼠并取不同的组织称重,检测血液中甘油三酯、葡萄糖、脂肪酸、炎症因子的水平。利用质谱方法检测血液中氨基酸的水平。结果:野生型小鼠皮下肿瘤种植2周后体重没有明显变化,脾脏和肝脏的重量明显增加,皮下脂肪组织和腹腔脂肪组织的重量没有明显变化。血液中甘油三酯的水平明显增高,葡萄糖和甘油的水平明显下降。血液中炎症因子Interleukin 6(IL6)和Interferon gamma(IFNγ)的水平明显增加。血液的质谱结果显示有四种氨基酸的水平有明显变化,其中胱氨酸(Cystine)增加了约30倍,丝氨酸(Serine)、谷氨酰胺(Glutamine)和色氨酸(Tryptophan)分别有不同程度的降低。结论:皮下黑色素瘤显著影响小鼠机体营养状态和炎症,并特异性影响血液中氨基酸的代谢。     

Ascorbic acid synthesis and concentrations in organs of copper-deficient and brindled mice

Copper deficiency was studied in mice to investigate an interaction between copper and ascorbic acid. Twelve-day-old mutant brindled mice that exhibited signs of copper deficiency were compared to their normal brothers as well as to age-matched suckling mice that were copper deficient (-Cu) because their dams were consuming a copper-deficient diet throughout gestation and lactation, and a fourth group of copper-supplemented ( + Cu) suckling mice that served as dietary controls. Dietary copper deficiency was also produced in older mice by beginning the treatment at birth and continuing for 7 wk. Organ ascorbate levels were determined by high performance liquid chromatography with electrochemical detection. Differences caused by diet and genetics were evident but age-dependent. Compared to controls, liver and kidney ascorbate levels did not change remarkably in young or old copper-deficient mice. Cardiac ascorbate levels were higher in 7-wk-old - Cu mice and lower in 12-d-old - Cu mice, despite hypertrophy in both cases. Spleen ascorbate levels were lower in older -Cu mice and higher in 12-d-old mice, but total spleen ascorbate reflected the hypertrophic and atrophic size in the older and younger -Cu mice, respectively. Brindled mutants had an extremely low level of ascorbate in spleen. Plasma ascorbate was lower in 7-wk-old - Cu mice. Reasons for the alterations in ascorbate levels are not known. Synthesis in liver from D-glucuronate was not altered by dietary copper deficiency in 7-wk-old mice. Synthesis was lower in livers from 12-d-old - Cu and brindled mice compared to control values. However, the difference correlated better with body weight of the mice rather than with degree of copper deficiency. Consequences of the altered organ levels of ascorbate in copper-deficient mice are not completely known.     

小鼠异常行为及其继代遗传特性

实验室条件下小鼠常表现多种异常行为,通过对跳跃爬行鼠和非跳跃爬行鼠的亲代及F1代的行为观察,研究小鼠异常行为在继代过程中的变化规律以及皮质醇浓度与异常行为的关系。结果表明:两代跳跃爬行鼠和非跳跃爬行鼠的异常行为差异显著(P<0.05),在正常行为中跳跃爬行鼠的平均睡眠时间和修饰行为的次数明显少于非跳跃爬行鼠(P<0.05),而探究行为的次数明显高于非跳跃爬行鼠(P<0.05)。F1代跳跃爬行鼠的异常行为类型基本和母体一致,异常行为的发生次数明显高于亲代,说明异常行为具有遗传基础。通过测定皮质醇浓度,发现跳跃爬行鼠的皮质醇平均浓度明显高于非跳跃爬行鼠(P<0.05),说明皮质醇的分泌量影响着异常行为的发生频率。     

Adipose Tissue-Derived Human Serum Amyloid A Does Not Affect Atherosclerotic Lesion Area in hSAA1+/?/ApoE?/? Mice

Chronically elevated serum levels of serum amyloid A (SAA) are linked to increased risk of cardiovascular disease. However, whether SAA is directly involved in atherosclerosis development is still not known. The aim of this study was to investigate the effects of adipose tissue-derived human SAA on atherosclerosis in mice. hSAA1^+/− transgenic mice (hSAA1 mice) with a specific expression of human SAA1 in adipose tissue were bred with ApoE-deficient mice. The hSAA1 mice and their wild type (wt) littermates were fed normal chow for 35 weeks. At the end of the experiment, the mice were euthanized and blood, gonadal adipose tissue and aortas were collected. Plasma levels of SAA, cholesterol and triglycerides were measured. Atherosclerotic lesion areas were analyzed in the aortic arch, the thoracic aorta and the abdominal aorta in en face preparations of aorta stained with Sudan IV. The human SAA protein was present in plasma from hSAA1 mice but undetectable in wt mice. Similar plasma levels of cholesterol and triglycerides were observed in hSAA1 mice and their wt controls. There were no differences in atherosclerotic lesion areas in any sections of the aorta in hSAA1 mice compared to wt mice. In conclusion, our data suggest that adipose tissue-derived human SAA does not influence atherosclerosis development in mice.     

A comparison of Babesia infections in intact,surgically splenectomised,and congenitally asplenic (Dh/+) mice

Infections with Babesia rodhaini and B. microti were studied in congenitally asplenic (Dh/+) mice, surgically splenectomised mice and intact mice. Mice without spleens were more susceptible to infections than intact mice, but Dh/+ mice were less susceptible than surgically splenectomised mice, indicating that some functional splenic activity had been taken over by other tissues in Dh/+ mice. It is suggested that this functional activity may be mediated by natural killer (NK) cells, and that Dh/+ mice could prove of value in the study of babesiosis in general and NK activity in particular.Male mice were more susceptible to infection than females.     

人DAF基因在转基因小鼠中的遗传与表达

为研究人ＤＡＦ基因在小鼠体内遗传与表达的规律,从质粒ｐＳＦＦＶ－ＤＡＦ分离出一段包含人ＤＡＦ基因的ＤＮＡ片段。采用受精卵显微注射法建立转人ＤＡＦ基因小鼠。提取出生小鼠的染色体ＤＮＡ,经Ｄｏｔ－ｂｌｏｔ与Ｓｏｕｔｈｅｒｎ－ｂｌｏｔ杂交相结合确定首建转基因小鼠,并经Ｄｏｔ－ｂｌｏｔ杂交研究人ＤＡＦ基因在转基因小鼠体内的遗传特征,Ｎｏｒｔｈｅｒｎ杂交确定其表达情况。小鼠受精卵经基因导入后,共生出２４只小鼠,其中４只被确定为首建转基因小鼠,整合率为１５％,在首建转基因小鼠两两交配生出的Ｆ１代小鼠中分别有７０％和７５％继续携带人ＤＡＦ基因。首建转基因小鼠中有１只小鼠在ＲＮＡ水平表达了人ＤＡＦ基因。可见,人ＤＡＦ基因整合入小鼠基因组中,并能够稳定遗传及表达。     

The use of dirty bedding for detection of murine pathogens in sentinel mice

Sentinel Swiss (CD-1) mice, housed without filter bonnets, were seronegative for mouse hepatitis virus (MHV) for 8 consecutive months in an experimental colony of CD-1 mice. MHV titers had been detected sporadically in sentinel mice housed in this colony during a 2 year period. In an effort to determine whether MHV was still present in the colony, two methods of exposing sentinel mice to an animal room environment were compared under routine husbandry practices. Eight cages (12 mice per cage; 2 cages per rack) of experimental virus antibody free sentinel mice, housed without filter bonnets, were placed on the bottom shelf of 4 of 12 racks in the room. Twice each week, four cages of sentinel mice received a composite sample of dirty bedding (bedding used previously by mice in the room). The remaining four cages of experimental sentinels received fresh non-used bedding. Sentinel mice were bled at monthly intervals for MHV serology. After 4 months, mice from two cages which received dirty bedding seroconverted to MHV and mice from one cage were positive for Myobia musculi (mites). Three weeks later, all four cages of mice which received dirty bedding were positive for MHV and three were positive for mites. In contrast, only two of four cages of mice which received fresh bedding were positive for MHV and all were negative for mites. These findings indicate the importance of exposing sentinel mice to dirty bedding and that MHV and mites may go undetected for several months in a mouse colony when the incidence levels are low where standard sanitation procedures are used.     

The differential responses to the odor of unfamiliar male conspecifics in dominant,subordinate, and isolated mice

Male ddY mice were used to investigate the responses toward the odor of unfamiliar male mice. They were reared either in isolation from 3 weeks of age or in pairs. At 10 weeks of age, they went through a 4-day test period, in which the responses of the mice toward the odor of unfamiliar dominant and subordinate mice were investigated by differentiating the responses into the time to investigate the odor and the final decision of avoidance or preference. All the mice went through the encounter tests after this odor test in order to investigate the relationship between the responses toward the odor and the behavior toward the odor donor. The pair-reared dominants and the subordinates responded to the odor of the dominant and subordinate mice differentially. This indicated that they could discriminate the dominance status of unfamiliar mice by odor. Isolated mice did not respond to the odor of the dominant and subordinate mice differentially. Social experiences were concluded to be necessary to discriminate the dominance status of unfamiliar mice through odor. The length of the investigation time and the final decision of avoidance or preference did not correlate in pair-reared or isolated mice, and these 2 scales were concluded to be different. But the dominant mice that investigated the odor for longer periods tended to show aggression in the later encounter test.     

The comparison of sensitivity of motion sickness between retinal degeneration fast mice and normal mice

Recent studies report that a conflict between information from the visual system and vestibular system is one of the main reasons for induction of motion sickness (MS). We may be able to clarify the integration mechanism of visual and vestibular information using an animal model with a visual defect, the retinal degeneration fast (rdf) mouse, and the role of vestibular information in the pathogenesis of MS. The rdf mice and wild-type Kunming mice were subjected to rotary stimulation to induce MS. Conditioned taste anorexia to saccharin solution and behavior score were used to observe the differences in MS sensitivity between two types of mice. The decrease in intake of saccharin solution and the behavior score in rdf mice were greater than those in normal mice. After rotatory stimulation, the reduction of intake mass and the behavior score were greater in rdf mice compared to those of normal mice. The rdf mice were more sensitive to rotation than normal mice. We conclude that visual information plays a role in the pathogenesis of MS. Visual information and vestibular information impact each other and integrate through certain channels in the central nervous system in mice.     

The actions of dichloroacetic acid on blood glucose, liver glycogen and fatty acid synthesis in obese-hyperglycaemic (ob/ob) and lean mice

Obese-hyperglycaemic mice and lean mice were injected with dichloroacetate to determine the significance of gluconeogenesis in maintaining the hyperglycaemia of obese mice and to investigate the effects of a fall in blood glucose on fatty acid synthesis. One hour after the second of two, hourly, injections of dichloroacetate the blood glucose concentrations in fed and starved lean mice were decreased, whereas in obese mice they were sharply increased. In obese and lean mice, both fed and starved, dichloroacetate decreased plasma lactate but insulin was unchanged. The quantity of liver glycogen was decreased in all dichloroacetate treated mice, with the largest falls in fed and starved obese mice, which had much larger glycogen stores than lean mice. Dichloroacetate treatment decreased the concentration of plasma non-esterified fatty acids in fed and starved obese mice and fed lean mice but not in starved lean mice. Fatty acid synthesis in white (inguinal, subcutaneous) adipose tissue was stimulated by dichloroacetate in fed obese mice and inhibited in fed lean mice. Fatty acid synthesis in brown adipose tissue (scapular) was faster than in white adipose tissue and was less affected by dichloroacetate although the changes were in the same direction as in white adipose tissue. We attribute the increased hyperglycaemia of obese mice treated with dichloroacetate to increased glycogenolysis coupled with a failure to secrete additional insulin in response to the raised blood glucose. This high blood glucose concentration in dichloroacetate treated obese mice may in turn explain the increased fatty acid synthesis in their white adipose tissue.