1) Oxygen consumption increased over twofold when a b3 adrenergic agonist that s
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1) Oxygen consumption increased over twofold when a b3 adrenergic agonist that stimulate UCP1 was injected into normal mice. This was not observed when the agonist was injected into the knockout mice. Explain these results.
2) The UCP-1 knockout mice were essentially normal except for increased lipid deposition in their adipose tissue. Explain why.
3) In one experiment, normal mice and UCP-1 knockout mice were placed in a cold (5°C) room overnight. The normal mice were able to maintain their body temperatures at 37°C even after 24 hours in the cold. But the body temperatures of the cold-exposed knockout mice decreased 10°C or more. Explain.
Case 23 The Role of Uncoupling Proteins in Obesit Focus concept The properties of adipose tissue factors that uncouple oxidative phosphorylation are discussed and possible links between uncoupling proteins and obesity are examined. Prerequisites Electron transport and oxidative phosphorylation. Mechanisms of uncoupling agents, such as 2,4-dinitrophenol. Fatty acid oxidation. Background Hibernating animals and human infants contain brown fat deposits, so-called because of the presence of large numbers of mitochondria, the site of electron transport and oxidative phosphorylation. In brown fat, given the appropriate stimulus, oxidative phosphorylation and electron transport can be uncoupled, causing energy to be dissipated as heat. The protein responsible for the uncoupling is a brown fat inner mitochondrial membrane protein previously named UCP (for uncoupling protein), but now referred to as UCP1, since a second uncoupling protein has since been discovered. Previous experiments have shown that UCP1 protects against cold and is involved in regulation of energy expenditure. The ability of UCP1 to stimulate the consumption of calories solely for the production of heat led some investigators to postulate that UCP1 was involved in regulating body weight. Scientists have always wondered why some people seem to be able to ingest a large number of calories without gaining weight, whereas others eat moderately but are obese. If the UCP1 of brown fat were involved, scientists postulated that obese people would be efficient "burners", whereas humans of moderate weight might burn calories inefficiently, releasing a greater proportion of energy as heat. But the role of UCP1 in humans has always been debated since infants contain a large amount of brown fat but mature adults do not. In order to examine the biochemical role of UCP1 more fully, the investigators in this case worked with mice referred to as knockouts. Knockout mice have been genetically engineered such that the gene coding for a particular protein is missing. By examining the characteristics of knockout mice, the biochemical and physiological roles of a particular protein can be ascertained. The investigators produced UCP1-knockout mice that are missing the gene for the UCP1 protein. They carried out experiments using these mice that are described below, studies that led to the discovery of a second uncoupling protein referred to as UCP2. The UCP2 protein may play a more significant role in obesity, since UCP2 is found in abundant amounts in white fatExplanation / Answer
Thermogenin (called uncoupling protein or uncoupling protein 1, or UCP1) is an uncoupling protein found in the mitochondria of brown adipose tissue (BAT). It is used to generate heat by non-shivering thermogenesis, and makes a quantitatively important contribution to countering heat loss in neonates & hibernating animals.
1) Oxygen consumption increased over twofold when a b3 adrenergic agonist that stimulate UCP1 was injected into normal mice. This was not observed when the agonist was injected into the knockout mice. Because knockout mice don’t have gene for b3 adrenergic receptor so it don’t stimulate UCP1. UCPs are transmembrane proteins that decrease the proton gradient generated in oxidative phosphorylation. They do this by increasing the permeability of the inner mitochondrial membrane, allowing protons that have been pumped into the intermembrane space to return to the mitochondrial matrix. UCP1-mediated heat generation in brown fat uncouples the respiratory chain, allowing for fast substrate oxidation with a low rate of ATP production.
2) More physical activity means less lipid deposition which means less obesity. Although physical activity is the dominant mechanism for dissipating excess energy, a system of thermogenesis that evolved to protect the body from hypothermia is based upon the uncoupling of oxidative phosphorylation in brown adipocytes by the mitochondrial uncoupling protein (UCP1). As UCP1 knockout mice don’t have UCP1 gene so they show uncoupling oxidative phosphorylation but other process in body remain same that’s why The UCP-1 knockout mice were essentially normal except for increased lipid deposition in their adipose tissue.
3) In one experiment, normal mice and UCP-1 knockout mice were placed in a cold (5°C) room overnight. The normal mice were able to maintain their body temperatures at 37°C even after 24 hours in the cold because normal mice have brown fat & it shows thermogenesis (heat generation) by the uncoupling of oxidative phosphorylation in brown adipocytes by the mitochondrial uncoupling protein (UCP1). While UCP1 knockout mice don’t have gene for uncoupling of oxidative phosphorylation so the body temperatures of the cold-exposed knockout mice decreased 10°C or more.
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