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      Increased obese mRNA expression in omental fat cells from massively obese humans.

      Nature medicine
      Adipose Tissue, metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Animals, Body Mass Index, Cell Size, Energy Metabolism, genetics, Female, Gene Expression Regulation, Humans, Leptin, Male, Mice, Mice, Inbred C57BL, Middle Aged, Obesity, pathology, Omentum, Protein Biosynthesis, Proteins, RNA, Messenger, biosynthesis

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          Abstract

          Obesity presents a significant challenge to the general health of affluent nations in terms of the number of people affected, the serious associated maladies and the lack of effective treatments. While common wisdom has held that obesity results from 'gluttony and sloth', a number of studies have indicated physiological causes of underlying the pathogenesis of obesity, with the degree of adiposity having a strong genetic component. Recently, the obese gene in the ob/ob mouse was cloned, along with its human homologue. The specific production of the obese protein by adipose tissue suggested that it may function in a feedback loop from fat tissue to the hypothalamus to control energy intake and/or energy expenditure, and that it may play a role in the pathogenesis of human obesity. In this study we report that obese mRNA expression is elevated in ex vivo omental adipocytes isolated from massively obese humans in the absence of an identifiable mutation. Therefore, we speculate that this increased expression may suggest that the massively obese are insensitive to the putative regulatory function(s) of the obese gene product.

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          Most cited references15

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          S Altschul (1990)
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            Changes in energy expenditure resulting from altered body weight.

            No current treatment for obesity reliably sustains weight loss, perhaps because compensatory metabolic processes resist the maintenance of the altered body weight. We examined the effects of experimental perturbations of body weight on energy expenditure to determine whether they lead to metabolic changes and whether obese subjects and those who have never been obese respond similarly. We repeatedly measured 24-hour total energy expenditure, resting and nonresting energy expenditure, and the thermic effect of feeding in 18 obese subjects and 23 subjects who had never been obese. The subjects were studied at their usual body weight and after losing 10 to 20 percent of their body weight by underfeeding or gaining 10 percent by overfeeding. Maintenance of a body weight at a level 10 percent or more below the initial weight was associated with a mean (+/- SD) reduction in total energy expenditure of 6 +/- 3 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 5 kcal per kilogram per day in the obese subjects (P < 0.001). Resting energy expenditure and nonresting energy expenditure each decreased 3 to 4 kcal per kilogram of fat-free mass per day in both groups of subjects. Maintenance of body weight at a level 10 percent above the usual weight was associated with an increase in total energy expenditure of 9 +/- 7 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 4 kcal per kilogram per day in the obese subjects (P < 0.001). The thermic effect of feeding and nonresting energy expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kilogram of fat-free mass per day, respectively, after weight gain. These changes in energy expenditure were not related to the degree of adiposity or the sex of the subjects. Maintenance of a reduced or elevated body weight is associated with compensatory changes in energy expenditure, which oppose the maintenance of a body weight that is different from the usual weight. These compensatory changes may account for the poor long-term efficacy of treatments for obesity.
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              Mitotic forces control a cell-cycle checkpoint.

              Every time a cell divides, the chromosomes must be distributed accurately to the daughter cells. Errors in distribution arise if chromosomes are improperly attached to the mitotic spindle. Improper attachment is detected by a cell-cycle checkpoint in many cells and the completion of cell division is delayed, allowing time for error correction. How is an improperly attached chromosome detected? An absence of tension from mitotic forces is one possibility. Here we test this possibility directly by applying tension to an improperly attached chromosome with a micromanipulation needle. In the absence of tension, the entry into anaphase and the completion of mitosis was delayed by 5-6 hours. When the misattached chromosome was placed under tension, however, the cell entered anaphase in 56 minutes, on average. Tension from mitotic forces or from a micromanipulator's needle evidently signals to the checkpoint that all is in order and that cell division can proceed.
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