Obese mice

Additional in vivo studies on the biological activity of proanthocyani-dins investigating a series of behavioral activities (motihty, body weight gain, body temperature, motoric coordination, anticonvulsant effects and central analgesic activities) showed no or only moderate pharmacological effects [53]. On the other hand, dietary supplementation with cocoa pro-cyanidin supplements can dose-dependently prevent the development of hyperglycemia in diabetic obese mice [54]. 

DGAT2- - mice suffer from severe hypolipidemia and do not survive postnatally [44]. However, this may be only a developmental phenomenon, since adult obese mice treated with DGAT2 antisense oligonucleotides were viable and showed improved hepatic steatosis along with improved insulin sensitivity [45]. 

Important studies were performed by Trush and coworkers [42], who showed the advantages of applying lucigenin-amplified CL for the measurement of superoxide production by mitochondria in unstimulated monocytes and macrophages as well as by isolated mitochondria [43,44]. Later on, these authors have shown that mitochondrial superoxide production measured by lucigenin-amplified CL increased in the liver of rats treated with the promoter of hepatocarcinogenesis ethinyl estradiol [45], in liver from obese mice [46], and in children with Down syndrome [47]. 

One of the classical obesity mntations in mice is termed ob, for obesity. Mice that are homozygous for the ob mutation (ob/ob mice) are grossly obese. Jeffrey Friedman at the Rockefeller University elucidated the defect in ob/ob mice in 1992. Specifically, the ob gene encodes a protein termed leptin.Leptin is prodnced in fat tissue and acts on the central nervous system at the hypothalamus. Basically, it reports nutritional information to this control center. 

Yang R, Castriota G, Chen Z et al (2011) RNAi-mediated germlme knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice. Int J Obes 35 217-225... 

Metabolism of carbon tetrachloride in obese mice, using three different models impact of differences metabolism on survival. 

Kalupahana, N. S., Claycombe, K., Newman, S. J., Stewart, T., Siriwardhana, N., Matthan, N., Lichtenstein, A. H., and Moustaid-Moussa, N. (2010b). Eicosapentaenoic acid prevents and reverses insulin resistance in high-fat diet-induced obese mice via modulation of adipose tissue inflammation. J. Nutr. 140,1915-1922. 

Le Marchand-Brustel, Y. Heydrick, S.J. Jullien, D. Gautier, N. Van Ob-berghen, E. Effect of insulin and insulin-like growth factor-I on glucose transport and its transporters in soleus muscle of lean and obese mice. Metab. Clin. Exp., 44, 18-23 (1995)... 

Uysal, K. T., et al., Improved glucose and lipid metabobsm in genetically obese mice lacking aP2. Endocrinology, 2000,141, 3388-3396. 

Murphy, J. E., Zhou, S., Giese, K., Williams, L. T., Escobedo, J. A. and Dwarki, V. J. (1997). Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin. Proc. Natl. Acad. Sci. USA 94, 13921-13926. 

Milk intake is measured in acute experiments in normal or obese mice after an overnight fast. Milk intake serves as a surrogate for food consumption. 

A description of testing protocols was not supplied by author. I. Body Mass Assay in Obese Mice Assay... 

Table 2 Effect on body fat mass and lean body mass for diet-induced obese mice using Entry 1 for 3 weeks at lOmg/kg per day...

Serotonin. Serotonin central receptors appear to play a major role in glucose homeostasis. Experiments in obese mice have demonstrated that small doses of a classical serotonin agonist, metachlorophenylpiperazine (mCPP), markedly lower plasma insulin levels and increase insulin sensitivity, without affecting food intake, body weight or fat mass. The downstream target of the involved serotonin receptor appears to be melanocortin-4 receptors, in the arcuate nucleus of the hypothalamus. 

Prokineticin 2. Recently discovered in the suprachiasmatic nucleus, prokineticin 2 is a signalling molecule that appears to help control hunger. Both lean and obese mice treated with prokineticin for five days lost almost 5% of their body weight. 

Fat loss. White adipose tissue is vascularised, much like a tumour, and growth of adipose tissue is highly dependent on the building of new blood vessels (angiogenesis). Recent studies with obese mice models have shown that proapoptotic peptide, directed against blood vessels, results in decreased food intake and significant fat loss. 

Leptin is a protein, encoded by the ob gene, first identified in obese mice. The ob gene is apparently expressed exclusively in white adipose tissue. Leptin binds to a receptor in the hypothalamus. 

Genetically obese mice were treated with fluoxetine to assess the ability of fluoxetine to produce weight loss. In this model, fluoxetine did produce initial weight loss but overtime had no positive impact on mouse weight. 

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