Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin is a hormone secreted by the adipocytes that regulates food intake and energy expenditure. It is known that growth hormone (GH) secretion is markedly influenced by body weight, being suppressed in obesity and cachexia, and recent data have demonstrated that GH release is regulated by leptin levels. Although one of the sites of action of leptin is likely to be the hypothalamus, since leptin receptor mRNA is particularly abundant in several hypothalamic nuclei, the mechanisms by which leptin regulates GH secretion are not yet known. The aim of the present study was to investigate whether leptin could act at the hypothalamic level modulating somatostatin and GH-releasing hormone (GHRH) expression. The administration of anti-GHRH serum (500 microl, i.v.) completely blocked leptin-induced GH release in fasting rats. In contrast, the treatment with anti-somatostatin serum (500 microl, i.v.) significantly increased GH release in this condition. Furthermore, leptin administration (10 microg, i.c.v.) to intact fasting animals reversed the inhibitory effect produced by fasting on GHRH mRNA levels in the arcuate nucleus of the hypothalamus, and increased somatostatin mRNA content in the periventricular nucleus. Finally, leptin administration (10 microgram, i.c.v.) to hypophysectomized fasting rats increased GHRH mRNA levels, and decreased somatostatin mRNA content, indicating an effect of leptin on hypothalamic GHRH- and somatostatin-producing neurons. These findings suggest a role for GHRH and somatostatin as mediators of leptin-induced GH secretion.
 ...
PMID:Role of growth hormone (GH)-releasing hormone and somatostatin on leptin-induced GH secretion. 989 45

Unexplained weight loss is common in patients with chronic obstructive pulmonary disease (COPD). Since leptin, an obesity gene product, is known to play important roles in the control of body weight and energy expenditure, we investigated serum leptin levels, along with circulating tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptor (sTNF-R55 and -R75) levels, in 31 patients with COPD and 15 age-matched healthy controls. The body mass index (BMI) and percent body fat (%fat) were significantly lower in the COPD patients than in the healthy controls (BMI = 18.1 +/- 2.7 kg/m2 versus 22.8 +/- 2.2 kg/m2 [mean +/- SD]; p < 0.0001; %fat = 16.9 +/- 5.8% versus 24.3 +/- 4.9%; p < 0.001). Serum leptin levels were significantly lower in the COPD patients than in the healthy controls (1.14 +/- 1.17 ng/ml versus 2.47 +/- 2.01 ng/ml; p < 0.05). In contrast, serum TNF-alpha levels (6.59 +/- 1.92 pg/ml versus 5.41 +/- 1.60 pg/ml; p < 0.05), plasma sTNF-R55 (1.16 +/- 0.47 ng/ml versus 0.67 +/- 0.13 ng/ml; p < 0.0001) and sTNF-R75 (3.65 +/- 1.29 ng/ml versus 2.25 +/- 0.43 ng/ml; p < 0.0001) levels were significantly higher in the COPD patients than in the healthy controls. Importantly, circulating leptin levels (log transformed) did correlate well with BMI and %fat, but not with TNF-alpha or with sTNF-R levels in the COPD patients. These data suggest that circulating leptin is independent of the TNF-alpha system and is regulated physiologically even in the presence of cachexia in patients with COPD.
 ...
PMID:Circulating leptin in patients with chronic obstructive pulmonary disease. 1019 68

Tumour necrosis factor-alpha (TNF) is a pleiotropic cytokine involved in many metabolic responses in both normal and pathophysiological states. In spite of the fact that this cytokine (also known as "cachectin") has been related to many of the metabolic abnormalities associated with cachexia, recent studies suggest that TNF may also have a central role in obesity modulating energy expenditure, fat deposition and insulin resistance. This review deals with the role of TNF in the control of fat mass and obesity.
 ...
PMID:Tumour necrosis factor, a key role in obesity? 1037 Nov 92

Progressive wasting is common in many types of cancer and is one of the most important factors leading to early death in cancer patients. Weight loss is a potent stimulus to food intake in normal humans and animals. The persistence of anorexia in cancer patients, therefore, implies a failure of this adaptive feeding response, although the weight loss in the patients differs from that found in simple starvation. Tremendous progress has been made in the last 5 years with regard to the regulation of feeding and body weight. It has been demonstrated that leptin, a hormone secreted by adipose tissue, is an integral component of the homeostatic loop of body weight regulation. Leptin acts to control food intake and energy expenditure via neuropeptidergic effector molecules within the hypothalamus. Complex interactions among the nervous, endocrine, and immune systems affect the loop and induce behavioral and metabolic responses. A number of cytokines, including tumor necrosis factor-alpha, interleukins 1 and 6, IFN-gamma, leukemia inhibitory factor, and ciliary neurotrophic factor have been proposed as mediators of the cachectic process. Cytokines may play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin. This could be done by persistent stimulation of anorexigenic neuropeptides such as corticotropin-releasing factor, as well as by inhibition of the neuropeptide Y orexigenic network that consists of opioid peptides and galanin, in addition to the newly identified melanin-concentrating hormone, orexin, and agouti-related peptide. Information is being gathered, although it is still insufficient, on such abnormalities in the hypothalamic neuropeptide circuitry in tumor-bearing animals that coincide with the development of anorexia and cachexia. Characterization of the feeding-associated gene products have revealed new biochemical pathways and molecular targets for pharmacological intervention that will likely lead to new treatments. Although therapeutic intervention using neuropeptide agonists/antagonists is now directed at obesity treatment, it may also have an effect on treating cancer anorexia-cachexia, especially when combined with other agents that have effects on muscle and protein breakdown.
 ...
PMID:Cancer anorexia-cachexia syndrome: are neuropeptides the key? 1049 94

Human subjects vary in the extent to which their body's protein and fat compartments are mobilized for fuel during starvation. Although an inverse association between the initial adiposity and the contribution of protein as fuel during starvation has been known for nearly a century, interest in the quantitative importance and functional significance of the initial percentage fat as a determinant of biological variation in energy-partitioning between protein and fat (and hence in determining the partitioning characteristic of the individual) is relatively recent. The present paper addresses these issues by revisiting the classic Minnesota experiment of semi-starvation and refeeding from a standpoint of system physiology. In a quantitative analysis of the relationship between the initial body composition (ration FAT0: fat-free mass (FFM)0) and the composition of weight loss (ratio delta FAT: delta FFM) in the thirty-two men in the Minnesota study, the arguments are put forward that the fraction of FFM lost when the fat stores reach total depletion is independent of the initial percentage fat, and that this fraction represents the 'dispensable' component of the protein compartment that is compatible with life (i.e. the protein energy-reserve, rp). The concepts are developed that (1) the initial percentage body fat (which reflects the initial ratio FAT0:FFM0) provides a 'memory of partitioning' which dictates the control of partitioning between protein and fat in such a way that both the protein energy-reserve (rp) and the fat energy-reserve (rf) each complete depletion simultaneously, a strategy that would ensure maximum length of survival during long-term food scarcity, and that (2) variability in the relative sizes of these two energy reserves (i.e. in rf:rp) could, in addition to the initial percentage fat, also contribute to human variability in energy-partitioning. The basic assumptions underlying this re-analysis of the Minnesota data, and the concepts that are derived from it, have been integrated in the simple mathematical model for predicting the partitioning characteristic of the individual. This model is used to explain how variability in the fraction of the protein compartment that could function as an energy reserve (rp) can be as important as the initial percentage fat in determining inter-individual variability in protein-sparing during the early phase of starvation, in fuel partitioning during prolonged starvation, or in the maximum percentage weight loss during starvation. The elucidation of factors underlying variability in the size of the protein energy-reserve may have important implications for our understanding of the pathophysiology of starvation and age-associated susceptibility to muscle wasting, and in the clinical management of cachexia and obesity.
 ...
PMID:The control of partitioning between protein and fat during human starvation: its internal determinants and biological significance. 1067 6

Non-insulin-dependent diabetes mellitus (type 2 diabetes) is known to be a polygenic and polyfactorial disorder. Here we describe the long-term examination of a transgenic mouse line showing the disruption of the leptin receptor (Lepr, Ob-R) gene caused by transgene insertion. The absence of the expression of the long isoform Ob-Rb uncovered a strong variation of the obesity and diabetes phenotype in the homozygous mutant mice of the outbred strain used. One part of the homozygous mice developed severe persistent early-onset obesity, whereas the other part developed cachexia after having shown initial obesity in the examination period up to 26 weeks p.p. The leptin-receptor-defective mice of this line might serve as a model for the investigation of genes modulating the development and mode of expression of diabetes.
 ...
PMID:Contrasting obesity phenotypes uncovered by partial leptin receptor gene deletion in transgenic mice. 1070 83

65 patients were examined. They were divided into three groups. Group 1 consisted of patients with anorexia nervosa (AN) without bulimia, complicated by cachexia and amenorrhea. Epileptoid personality masculinous body built and behaviour, essential disturbances of sexual self-identification prevailed in this group. 3 patients had homoerotic tendencies, while a syndrome of sex negation developed in 5 cases. In group 2 bulimia was a stage of AN development. The patients had frequently initial endocrinopathy (obesity, dysmenorrhea), experiences of phobia and anxiety, asynchronous disharmonious type of psychosexual ontogenesis. Group 3 of patients was characterized by predomination of bulimia symptoms as a variation of the disease course. Normostenic body built, normal somatoendocrine and psychosexual development were combined with hysteric personal characteristics, mood and sexual fluctuations.
 ...
PMID:[Specific factors of sex behavior in patients with anorexia nervosa and bulimia]. 1084 61

The introduction of HAART has changed the nutritional status of HIV patients. In the pre-protease inhibitor (PI) era, more than 60% of HIV-positive persons presented with protein energy malnutrition (PEM) and vitamin and mineral deficit. This caused progressive physical-metabolic wasting (wasting syndrome/cachexia) and increased susceptibility to opportunistic infections and drug toxicity. PEM was a concurrent cause in 80% of deaths attributed to AIDS. Since 1996, the year in which PIs were introduced, the number of patients dying as a result of AIDS has decreased by two thirds, and cachexia is no longer the AIDS terminal phase in developed countries. But different patterns of nutritional status changes have appeared in association with the use of newer anti-HIV therapies and with longer survival of HIV-infected patients. A new clinical and laboratory syndrome--lipodystrophy syndrome--now affects patients receiving PI-based therapy. This syndrome consists of changes in body shape that are caused by an abnormal redistribution of fat. Fat accumulates in the abdominal area (truncal and visceral obesity), in the axillary pads (bilateral symmetric lipomatosis), and in the dorsocervical pads ("buffalo hump," "bull neck") but decreases in the legs, arms, and nasolabial and cheek pads (peripheral lipodystrophy). Hyperlipidemia and insulin resistance are also frequently present (metabolic syndrome X). Pathogenic mechanisms of lipid and fat tissue disturbances are discussed in this article, and the clinical approach to patient management and therapeutic options for lipodystrophy and lipid dysmetabolism is evaluated.
 ...
PMID:Reversal of cachexia in patients treated with potent antiretroviral therapy. 1088 68

The diaphragm as a striated muscle is characterized by the repetition of a single element arranged in series: the sarcomere containing two kinds of myofilaments: a thick one constituted by the myosin, and a thin one primarily composed of actin. The myosin molecule consists of two heads where two myosin heavy chains (MHC) are fixed, a flexible hinge with two light (MLC) chains, and long rod-shaped tails. The diaphragm contains 4 MHC isoforms (MHC-slow, MHC-2A, MHC-2B, MHC-2X) and 6 MLC isoforms (MLC-1f, MLC-3f, MLC-1sa, MLC-1sb, MLC-2f, MLC-2s/v). In humans, the diaphragm contains mainly fibers expressing the isoforms MHC-slow, MHC-2A, and MLC-2f, MLC-2s et MLC-1f. For the mechanical properties of the different isoforms, there is a gradient from the MHC-slow to the MHC-2A, MHC-2B and MHC-2X/2B. According to the circumstances, the diaphragm will adapt towards a slow profile (COPD, cardiac failure and in animals: Duchenne muscular dystrophy, denervation-1 week, age-female, corticosteroids, chronic stimulation), or a fast profile (in animals: chronic hypoxia, denervation-2 weeks, age-males) or a more oxidative profile (in animals: cachexia, obesity). The reasons why the diaphragm adapts towards a slower or a faster muscle are not known. In fact, for a given pathological situation, several factors are able to influence the fiber composition of the diaphragm. Therefore, the net result of the influence of these different factors in terms of MHC and MLC diaphragm adaptation is difficult to predict.
 ...
PMID:[Clinical relevance of myosin isoforms in the diaphragm]. 1093 18

Clinical and experimental studies have implicated high circulating levels of the cytokine tumour necrosis factor-alpha (TNF-alpha) in the pathogenesis of insulin resistance, not only in obesity and diabetes, but also in clinical conditions associated with cachexia and sepsis. TNF-alpha impairs insulin-mediated glucose uptake in adipocytes, but because of lipolytic effects the interpretation of clinical studies and the extent to which TNF-alpha affects muscle insulin sensitivity are unclear. In addition, protein kinase C (PKC) has recently been implicated in the mechanism of TNF-alpha-induced insulin resistance. The present study investigated the effects of TNF-alpha and a PKC inhibitor (RO-318220) on basal and insulin-stimulated 2-[(3)H]deoxyglucose uptake in cultured L6 myoblasts. Reverse transcriptase-PCR analysis confirmed that L6 myoblasts express TNF-alpha receptors I and II (p60 and p80). Dose-response curves for glucose uptake were fitted to a quadratic function to derive C(I-150) values (concentration of insulin required to increase glucose uptake by 50%). Incubation with TNF-alpha at 1 or 10 ng/ml for 24 h had no significant effect on basal glucose uptake, insulin sensitivity or maximal insulin responsiveness. C(I-150) values (means+/-S.E.M.) were as follows: basal, 91.2+/-13 nM; 1 ng/ml TNF-alpha, 102+/-12 nM; and basal, 70.8+/-13 nM; 10 ng/ml TNF-alpha, 43.7+/-40 nM. PKC inhibition markedly attenuated glucose uptake, but there was no difference in insulin sensitivity with RO-318220 alone compared with RO-318220+TNF-alpha. In conclusion, although increased TNF-alpha expression and plasma concentrations have been implicated in the pathogenesis of insulin resistance in various clinical states, there is no evidence that TNF-alpha impairs insulin-stimulated glucose uptake in a skeletal-muscle-derived cell line.
 ...
PMID:Effects of tumour necrosis factor-alpha and inhibition of protein kinase C on glucose uptake in L6 myoblasts. 1099 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>