Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis (original) (raw)
Related papers
Hypothalamic and pituitary catecholamine levels in genetically obese mice (obob)
Brain Research, 1977
The genetically obese (obob) mouse has been widely investigated as a possible model for human obesity and related pathology 7. The syndrome observed in the obob is characterized by overeating, adiposity, hyperglycemia, insulin resistance and impairments of thermoregulation, thyroid and reproductive function 7,19-~1. The primary defect responsible for the syndrome has yet to be discovered. Much recent work, however, has been devoted to evaluation of the hypothalamic-pituitary axis in these animals. In comparison to lean littermates, both male and female obob mice have lower levels of pituitary prolactin (PRL) z3,35. Pituitary levels of luteinizing hormone (LH) are also reported to be significantly lower in obob mice than in lean controls 36, but growth hormone (GH) and follicle-stimulating hormone (FSH) levels appear to be as high or higher in obob mice as in lean controls 23,35,36. Serum levels of PRL, LH, GH, and FSH are all reported to be lower in obob mice than in lean littermates ~a,35,3~. Furthermore, there is evidence to indicate that ACTH levels may be chronically elevated in the obob al. The observations that pituitary levels of some hormones are high while serum levels are low suggest that the obob may have deficits in both the synthesis and release of pituitary hormones. Similarities have been noted between the spontaneously obese obob mouse and animals with brain-lesion produced obesity such as the ventromedial hypothalamic rat or the gold thioglucose (GTG) injected mouseT,1L Serum GH and PRL concentrations, for example, are reported to be lower in the GTG mouse 3°,35. No naturally occurring hypothalamic lesions have been reported in the obob mousel°,~t,l'~'; however, significantly elevated levels of hypothalamic norepinephrine (NE) have recently been found 25,~n. Many studies suggest that an important function of hypothalamic monoamines is the control of pituitary hormone releasO ,a2,16,33,38. Infusions of biogenic amines have been shown to inhibit or induce the release of anterior pituitary hormones 6,28,29, 33. In addition, changes both in fluorescence of hypothalamic catecholamine-containing neurons and in the activity of related enzymes have been reported to follow alterations in endocrine states 17,2z,24.
Neuroscience and biobehavioural reviews, 2001
In small rodents there is compelling evidence of a lipostatic system of body mass regulation in which peripheral signals of energy storage are decoded in the hypothalamus. The ability of small mammals to defend an appropriate mass against imposed energy imbalance has implicated hypothalamic neuroendocrine systems in body mass regulation. The effect of the neuropeptide systems involved in this regulation is primarily compensatory. However, small mammals can also effect changes in the level of body mass that they will defend, as exempli®ed by seasonal species. Regulatory control over fat mass may be relatively loose in humans; the sizes of long-term storage depots may not themselves be regulated, but rather may be a consequence of temporal variations in the matching of supply and demand. Whether food intake is regulated to match energy demand, or to match demand and to regulate storage, it is clear that physiological defects or genetic variation in hypothalamic and peripheral feedback systems will have profound implications for fat storage. Study of mechanisms implicated in energy homeostasis in laboratory rodents is likely to continue to identify targets for pharmacological manipulation in the management of human obesity. q
Recent patents on CNS drug discovery, 2006
Obesity has reached epidemic proportions across the developed world. Even though there have been numerous scientific advances in terms of the understanding of the regulation of energy homeostasis, few novel anti-obesity drugs have emerged. Furthermore, those that are available have limited efficacy in producing and maintaining a weight loss beyond 10%. This is partly attributable to the complex neuronal circuitry at play within the central nervous system and periphery, which acts to regulate food intake and energy expenditure. This article will focus on a selection of the many products (peptides, neurotransmitters and others) such as endocannabinoids, Neuropeptide Y, Orexins, Melanin-Concentrating Hormone, Melanocortins, Cocaine and Amphetamine Regulated Transcript and Serotonin, expressed within the brain, that have been shown to influence energy balance. The true relevance of many of these to the regulation of human energy balance remains uncertain, but some novel anti-obesity dru...
Commentary on Classics of Obesity 4. Hypothalamic Obesity
Obesity Research, 1993
The fourth Classic in (3-esity comprises three papers, each dealing with obesity and hypothalamic or pituitary disease. The published versions are translations of a paper by Bernard Mohr (1809-1848) entitled, "Hypertrophy of the Hypophysis Cerebri and its Pressure on the Ventral Brain Surface, particularly on the Optic Tract and Chiasm of the Left Hemisphere," a paper by Joseph Francois Felix Babinski (1857-1932) entitled, "Tumor of the Pituitary Body without Acromegaly and with the Arrest of the Genital Organs," and a translation by Hilda Bruch of the paper by Alfred Frohlich (1871-1953) entitled, "A Case of Tumor of the Hypophysis without Acromegaly." The earliest of these three cases was published in 1840 by Mohr (1 8) and is sometimes credited as the initial description of the pituitary tumor as the cause of obesity. Although there was an association between the pituitary tumor in an overweight individual, a cause and effect relationship was not suggested by the author nor was there any evidence of a temporal relationship between the pituitary disease and the patient's weight gain. A second paper by Rayer (20) has also been identified as a paper relating pituitary tumors and obesity. On reading this paper, there is no identification of obesity among the cases with pituitary tumors. It is thus more appropriate to accord recognition for the association between a pituitary tumor and obesity to the two papers by Frohlich (12) and Babinski (2). With the advent of frequent autopsy examination at the beginning of the 19th century, many reports of diseases involving the pituitary and hypothalamus began to appear (17). These can be grouped into several categories (6), including inflammatory lesions, hemorrhagic lesions, cysts, and a variety of tumors. Recognition that a disorder of the pituitary could produce generalized systematic symptoms goes to Pierre Marie (16) for his description of acromegaly in 1886.
Causes of obesity: Looking beyond the hypothalamus
Progress in Neurobiology, 2007
The brain takes a primary position in the organism. We present the novel view that the brain gives priority to controlling its own adenosine triphosphate (ATP) concentration. It fulfils this tenet by orchestrating metabolism in the organism. The brain activates an energy-on-request system that directly couples cerebral supply with cerebral need. The request system is hierarchically organized among the cerebral hemispheres, the hypothalamus, and peripheral somatomotor, autonomic-visceromotor, and the neuroendocrine-secretomotor neurons. The system initiates allocative behavior (i.e. allocation of energy from body to brain), ingestive behavior (intake of energy from the immediate environment), or exploratory behavior (foraging in the distant environment). Cerebral projections coordinate all three behavioral strategies in such a way that the brain's energy supply is guaranteed continuously. In an ongoing learning process, the brain's request system adapts to various environmental conditions and stressful challenges. Disruption of a cerebral energy-request pathway is critical to the development of obesity: if the brain fails to receive sufficient energy from the peripheral body, it compensates for the undersupply by increasing energy intake from the immediate environment, leaving the body with a surplus. Obesity develops in the long term. #
International Textbook of Obesity
Table 14.1 Animal models of obesity and diabetes Classification of animal models of obesity and diabetes Examples of models/methods Spontaneous, naturally occurring-of unknown genetic/physiologic causes Probable genetic Gene-gene interactions Gene-environment interactions Aging-associated e.g. non-human primates, aging Sprague-Dawley rats Specific genetic models of single gene mutations of known or unknown function (spontaneous, bred, or transgenic) Ob/ob mouse Db/db mouse Fa/fa rat Tub mouse Ay mouse Others Dietary induced obesity High fat diet fed rodents 'Cafeteria' (highly palatable) diet fed rodents Neuroendocrine disorders Hypothalamic or related brain area lesions or stimulation (including electrolytic, knife cut, chemical, viral) 182 INTERNATIONAL TEXTBOOK OF OBESITY 183 OBESITY IN ANIMAL MODELS 184 INTERNATIONAL TEXTBOOK OF OBESITY
Glucocorticoid-dependency of increased adiposity in a model of hypothalamic obesity
Neuro endocrinology letters
It is known that rats treated, at neonatal age, with monosodium L-glutamate (MSG) develop neuroendocrine and metabolic abnormalities, resulting in a phenotype of hypothalamic obesity, characterized by increased adiposity, corticosteronemia and leptinemia. We explored whether adrenal manipulations could result in the reversion of this phenotype of hypothalamic obesity. Newborn male rats, treated with MSG or vehicle (CTR), were submitted to sham operation, bilateral adrenalectomy (ADX) or bilateral adrenal enucleation (AE) on day 120 of age. Animals were examined 21 days after ADX, combined or not with corticosterone (B) substitution (ADX+B), and on days 21 and 35 after AE. Food intake, body weight and body fat mass were monitored; additionally circulating levels of insulin, leptin, ACTH and B were measured. Our data indicate that: a) normalization of basal B circulating levels in, 21 day-ADX and -AE, MSG rats fully reversed hyperinsulinemia, hyperleptinemia and significantly decrease...
The Effects of High-Fat Diet on the Mouse Hypothalamus: A Stereological Study
Unbiased Stereology of Neural Systems, 2013
It has been demonstrated that the type of diet affects the brain structure and function. Consumption of fat-rich food is one of the most important factors that lead to increase in the prevalence of cardiovascular and neurological diseases. High-fat diet may change the volume and neuronal number or density in the hypothalamus, which is the center of energy control. Therefore, this study was designed to study the effect of high-fat diet on the density and number of neurons, and also the volume of hypothalamus in adult male mice. Forty male mice were divided into the control and experimental groups. The control group were fed with standard and the experimental groups, with high-fat diet for 4 (short-term) or 8 (long-term) weeks. The animals were perfused and brains were immediately removed, post-fixed and cut coronally and serially using cryostat at 30-µm thickness. Every 6th sections were stained by cresyl violet. The numerical density and number of neuron and the volume of hypothalamus were estimated by using unbiased stereological methods. Data analysis showed that both short and long time consumption of high-fat diet decreased the neuronal cell density of the hypothalamus. Interestingly, despite a decrease in the neuronal cell density, long time consumption of high-fat diet could significantly increase the volume of hypothalamus (P<0.05). High fat diet decreased the neuronal cell density and increased the volume of the hypothalamus, but it did not significantly change its total neurons. These changes might be due to an increase in the extracellular space through inflammation or gliosis in the hypothalamus. mass index (BMI) greater than 30 kg/m 2 [2] that results from an imbalance between caloric intake and energy expenditure . The prevalence of obesity in the majority of countries has increased in the last ten years . This indicates that primary cause of obesity is related to the environmental, social and beha vioral changes, although genetic factors may also be involved . Consumption of dietary fats is amongst the most important environmental factors leading to obesity . High-fat diets in rodents are generally considered to produce obesity, similar to that seen in humans. High-fat diets in the literatures are labeled such when fat composition is anywhere High-fat diet effect on the hypothalamus in stereotaxic coordinates http://dx.
Central catecholamine levels in genetically obese mice (obob and dbdb)
Brain Research, 1975
Genetically obese mice have been available for study for many years, but the cause of the obesity remains obscure. A number of similarities between genetically transmitted obesity and hypothalamic lesion-induced obesity have been reported, and the hypothalamus has been proposed as the locus of a genetic lesion responsible for obesity in both the obob and dbdb mutants 4-6. Norepinephrine (NE), a catechol-