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Gold thioglucose obesity syndrome.

Parenteral administration of gold thioglucose to mice produces an area or necrosis in the ventromedial portion of the hypothalamus. The lesion, like lesions produced by electrocautery of this area, causes hyperphagia and consequent obesity. The glucose moiety of gold thioglucose is essential for production of the lesion. Glucose analogues (2-deoxy-glucose, sodium thioglucose and phlorizin) prevent the gold thioglucose-induced lesion, and by themselves produce a transient hyperphagia. Insulin deficiency prevents the lesion. Either adrenalectomy or hypophysectomy counteracts the effect of insulin deficiency. Electron microscopic studies, in which general necrosis is avoided by administration of aspirin before gold thioglucose or by administration of subnecrotic doses of gold thioglucose, reveal that gold thioglucose primarily affects neural elements contiguous with capillaries in the ventromedial hypothalamus. The experimental observations indicate the presence of special glucoreceptor cells in the ventromedial hypothalamus that are involved in the regulation of food intake.

Adrenalectomy

[Physiological equilibration of water, electrolytes and nutrients].

An account is given of the fundamental mechanisms concerned with the regulation of hunger and thirst, and of the physiological processes involved in the uptake of nutrients, water and electrolytes. Several reflex chains ensure that the organism does not take up too much water and also protect it from excessive loss of water and salt.

Adult

Anorexia-producing intermediary metabolites.

Major phases of the physiology of food intake regulation remain hypothetical. There is a central regulatory mechanism for hunger and satiety, but the signals and messages that activate the brain centers remain conjectural. The alimentary tract regulation, the regulation by osmoreceptors, the thermostatic, the glucostatic, the lipostatic, the amino acid, and the hormonal food intake regulation theories leave many questions unanswered. Low molecular weight peptides appear to have an important effect on brain functions. Hypothalamic peptides such as thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin have been assigned new roles in various brain functions. The hypothalamus and probably other parts of the brain produce also anorexigenic peptides. Anorexia is a common manifestation of cancer. It is proposed that peptides, oligonucleotides, and other small metabolites produced by the cancer and by the tumor-bearing host are responsible for the genesis of the anorexia. They produce the anorexia through a peripheral effect on neuroendocrine cells and neuroreceptors and through a direct effect on hypothalamic and other central nervous system sensor and responder cells.

Animals

[Mechanisms of dietary selection in man: preferences and aversions].

Ingestion of food and water is the most important mean by which an animal maintains the integrity of the "milieu interne". In a free feeding situation the animal selects the nutrients demanded by the monitors of the internal fluid environment and avoids the malaise caused by ingested toxins; to doing, it maintains the constancy of its body composition. The essential features of this qualitative regulation have been extensively studied in the animal: the choice of nutrient is based on the sensory activity of the ingested material at the oropharynegeal level; some preferences and aversions are innate; others are acquired by conditioning; conditioned taste aversions can be acquired after a single association between the conditioned stimulus (taste) and the unconditioned one (malaise); some preferences and aversions are acquired slowly under the reenforcing effect of the nutritional activity of the ingested food. Are the same characteristics found in man? Studies in man are not numerous but it seems that the same mecanisms are patent in the neonate, the young child and the adult in a distressful situation. On the contrary, in a free feeding situation, sociocultural factors are prevalent.

Adult

Long-and short-term regulation of feeding patterns in the rat.

Analysis of feeding patterns in rats showed that the amount of food eaten in relatively long intervals (24-72 hr) was correlated with mean meal size and was essentially uncorrelated with meal frequency. Similarly, the regulatory adjustment in daily food intake occurring in response to changes in environmental temperature was shown to be the result of an adjustment in mean meal size, with no change in meal frequency. On the other hand, the amount of food eaten in relatively short intervals (3-12 hr) was shown to be more highly correlated with meal frequency than with mean meal size, and a reliable correlation between meal size and the postmeal interval was obtained. It was also shown that the meal size/postmeal interval regression equation predicts the long-term relation between mean meal size and the amount of food eaten. Take together, these results indicate that meal frequency is controlled largely by short-term regulatory signals and that at least some long-term regulatory signals affect meal size directly.

Animals

Impaired leptin A signaling disrupts hepatic lipid metabolism and growth in female medaka (Oryzias latipes).

Leptin is a central regulator of appetite and energy metabolism in vertebrates, and its deficiency in mammals typically results in hyperphagia and severe obesity. In fish, however, the physiological roles of leptin remain less clearly defined, partly due to the whole genome duplication (WGD) and divergent expression patterns. In this study, we generated a leptin A (lepa) loss-of-function mutant in medaka (Oryzias latipes) using CRISPR/Cas9 to investigate the function of leptin signaling. Phenotypic analysis revealed that female homozygous mutants exhibited significantly reduced body length and body weight compared with wild-type females, indicating growth impairment. Unexpectedly, despite their lean phenotype, the female mutants developed pronounced hepatic steatosis accompanied by the formation of spongiosis hepatis structures, while no obvious fibrosis was detected. To explore the molecular mechanisms underlying these abnormalities, transcriptomic profiling of mutant livers was performed. Differentially expressed genes were significantly enriched in pathways related to lipid metabolism, including Fatty acid metabolism and PPAR signaling pathway, suggesting a potential reduction in hepatic fatty acid β-oxidation capacity. In addition, genes involved in endoplasmic reticulum stress, autophagy, and apoptosis were altered, indicating transcriptional changes in cellular stress-response pathways under leptin A deficiency. Together, these findings suggest that leptin A may play an important role in coordinating growth and hepatic lipid metabolism in medaka and highlight potential differences in leptin-mediated metabolic regulation between fish and mammals.

Animals

Basic considerations in the treatment of obesity.

The recognition and treatment of obesity has undergone marked changes in the past two decades. Along with the abandoning of the concept of exogenous obesity, the physician has discovered a variety of developmental, psychological, pharmacologic, socioeconomic, neurological, and genetic roots for the syndrome. The clinician has also found medical treatment modalities (fasting and behavior modification) that hold much more promise than traditional supportive relationships with dietary consultation and anorexogenic medications. Surgical treatment also, ileojejunal bypass, is gradually emerging as a treatment of choice for certain well-motivated, super-obese people for whom all other treatment modalities have failed. Future research into central serotonergic mechanisms offers hope that we can begin to know what it is that turns on hunger, turns off appetite, and regulates weight in such a stable manner over such a long period of time.

Adolescent

Vagotomy for treatment of severe obesity.

Three women weighing 137, 133, and 135 kg underwent truncal vagotomy; after 16, 20, and 24 weeks they had lost 10, 17, and 19 kg respectively without serious side-effects. No dietary restrictions have been imposed, but they are eating less than they were preoperatively and report a total lack of hunger. Truncal vagotomy may be a useful treatment for severe obesity.

Adult