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diphtheria/lihavuus

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Brown adipose tissue-deficient [uncoupling protein (UCP)-promoter-driven diphtheria toxin A (DTA)] mice develop obesity as a result of both decreased energy expenditure and hyperphagia. The hyperphagia occurs despite high serum leptin levels. Hence, this is a model of leptin-resistant obesity in

Raising at thermoneutrality prevents obesity and hyperphagia in BAT-ablated transgenic mice.

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Transgenic mice with ablation of brown adipocytes induced by brown adipocyte-specific expression of diphtheria toxin A chain (DTA) driven by the uncoupling protein (UCP) promoter (UCP-DTA mice) become obese and hyperphagic (Lowell, B. B., V. S. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B.

Targeted expression of a toxin gene to adipose tissue: transgenic mice resistant to obesity.

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Obesity is characterized by increased adipose tissue mass and is often accompanied by a number of other disorders, such as diabetes, hypertension, and hyperlipidemia. To investigate the interrelationship between excessive adipose tissue mass and these associated disorders, we have attempted to

Mitochondria uncoupling proteins and obesity: molecular and genetic aspects of UCP1.

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Genetic variation in brwon fat specific mitochondrial uncoupling protein-1 (UCP1) expression and brown adipocyte morphology, have provided models to test the hypothesis that nonshivering thermogenesis is associated with the regulation of body weight. Genetic manipulation using transgenic animals and

Ciliary neurotrophic factorAx15 alters energy homeostasis, decreases body weight, and improves metabolic control in diet-induced obese and UCP1-DTA mice.

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Ciliary neurotrophic factor (CNTF) potently reduces appetite and body weight in rodents and humans. We studied the short- and long-term effects of CNTF(Ax15), a second-generation CNTF analog, in diet-induced obese C57BL/6J mice and brown adipose tissue (BAT)-deficient obese UCP1-DTA (uncoupling

Temperature-dependent feeding: lack of role for leptin and defect in brown adipose tissue-ablated obese mice.

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The objective was to characterize the ability of control and transgenic brown adipose tissue (BAT)-ablated uncoupling protein diphtheria toxin A chain (UCP-DTA) mice to adjust food intake in relation to changes in environmental temperature and to assess the involvement of leptin in this adjustment.
Brown adipose tissue (BAT) has the capacity for uncoupled mitochondrial respiration and is proposed to be a key site for regulating energy expenditure in rodents. To better define the role of BAT in energy homeostasis, we previously created a line of transgenic mice with deficiency of BAT (UCP

Regulation of lymphatic function and injury by nitrosative stress in obese mice

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Introduction: Obesity results in lymphatic dysfunction, but the cellular mechanisms that mediate this effect remain largely unknown. Previous studies in obese mice have shown that inducible nitric oxide synthase-expressing

Interleukin 2 receptor targeted fusion toxin (DAB486-IL-2) treatment blocks diabetogenic autoimmunity in non-obese diabetic mice.

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Insulin-dependent diabetes mellitus (IDDM) is strikingly similar in the non-obese diabetic (NOD) mouse and humans. In IDDM, the systematic autoimmune destruction of insulin-producing beta cells within the pancreas is dependent on autoreactive T cells. This autoimmune process can be accelerated by

Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature.

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We investigated the physiological basis for development of obesity in uncoupling protein-diphtheria toxin A chain (UCP-DTA) transgenic mice. In these mice the promoter of the brown adipose tissue (BAT)-specific UCP was used to drive expression of DTA, resulting in decreased BAT function and

Regulation of PPAR gamma gene expression by nutrition and obesity in rodents.

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The orphan nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma, is implicated in mediating expression of fat-specific genes and in activating the program of adipocyte differentiation. The potential for regulation of PPAR gamma gene expression in vivo is unknown. We cloned a

Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia.

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Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice. We

Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals.

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Obese adipose tissue is characterized by infiltration of macrophages. We and others recently showed that a specific subset of macrophages is recruited to obese adipose and muscle tissue. This subset expresses CD11c and produces high levels of proinflammatory cytokines that are linked to the

Paraventricular nucleus Sim1 neuron ablation mediated obesity is resistant to high fat diet.

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Single minded 1 (SIM1) is a transcription factor involved in brain patterning and control of energy balance. In humans, haploinsufficiency of SIM1 causes early-onset obesity. Mice deficient in the homologous gene, SIM1, also exhibit early onset obesity and increased sensitivity to a high fat diet.

A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages.

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Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood-brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous
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