Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adipocyte-derived hormone, leptin controls feeding behavior, augments fatty acid beta-oxidation in the skeletal muscle, attenuates insulin secretion but enhances whole body insulin sensitivity and glucose disposal, thereby serving as a promising therapeutic candidate for the treatment of insulin resistance and dyslipidemia. Along with other researchers, we demonstrated the clinical efficacy and safety of leptin in the treatment of diabetes and dyslipidemia for patients with generalized lipodystrophy. However, the clinical application of leptin has been hampered by the notion that leptin does not fully exert its metabolic effects in human obesity and diet-induced obese rodents. We found that the activity of skeletal muscle AMP-activated protein kinase (AMPK) parallels hypothalamic leptin sensitivity and metabolic phenotype in transgenic mice overexpressing leptin. Our data indicate that the activation of skeletal muscle AMPK is mediated by the hypothalamic melanocortin pathway. In fact, intracerebroventricular administration of melanocortin agonist, MT-II in mice robustly overcomes high-fat diet-induced leptin resistance and ameliorates fuel dyshomeostasis and hyperphagia, with a concomitant recovery of AMPK activity in skeletal muscle. Conversely, AMPK/ACC phosphorylation by leptin was abrogated by the co-administration of melanocortin antagonist, SHU9119 and in the KKA(y) mice, which centrally express endogenous melanocortin antagonist. Importantly, high-fat diet-induced attenuation of AMPK/ACC phosphorylation in leptin-overexpressing transgenic mice was not reversed by central leptin per se, but was markedly recovered by MT-II. Our data provide evidence for the critical role of the central melanocortin system in leptin-skeletal muscle AMPK axis, and highlight the system as a therapeutic target for leptin insuffciency in obese humans.
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PMID:Hypothalamic melanocortin signaling and leptin resistance--perspective of therapeutic application for obesity-diabetes syndrome. 1939 82

The antidiabetic therapeutic effect of Ecklonia cava, a brown alga, was investigated using streptozotocin-induced type 1 diabetes mellitus rats and C2C12 myoblasts. The methanol extract of E. cava (ECM), having a strong radical scavenging activity, significantly reduced plasma glucose level and increased insulin concentration in type 1 diabetes mellitus rats. Moreover, the elevation of plasma ALT in diabetic rats was dramatically restored near to normal range by the treatment of ECM, whereas AST level was not meaningfully altered in any group throughout the experiment. The characteristic indications of diabetes, such as polyphagia and polydipsia, were greatly improved by ECM treatment as well. The mechanism of action of ECM appears to be, at least partially, mediated by the activation of both AMP-activated protein kinase/ACC and PI-3 kinase/Akt signal pathways. Taken together, the present results suggest that E. cava has both in vivo and in vitro antidiabetic effects.
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PMID:Brown alga Ecklonia cava attenuates type 1 diabetes by activating AMPK and Akt signaling pathways. 1991 68

Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDEs), and one approach to solve this is careful matching of treatment to the specific pathologies of MDE. One such biological abnormality is elevated monoamine oxidase A (MAO-A) levels, which occurs in the prefrontal and anterior cingulate cortex (PFC and ACC) during MDE; however, the subtypes for which this abnormality is most prominent are unknown. We hypothesized that MAO-A levels in the PFC and ACC are most elevated in MDE with greater severity and reversed neurovegetative symptoms (hypersomnia and either hyperphagia or weight gain). MAO-A VT (an index of MAO-A density) was measured using [(11)C]harmine positron emission tomography (PET) in 42 subjects with MDEs secondary to major depressive disorder and 37 healthy controls. The effect of severity and reversed neurovegetative symptoms on MAO-A VT in the PFC and ACC was analyzed using a multivariate analysis of variance (MANOVA). Greater severity and reversed neurovegetative symptoms were associated with elevated MAO-A VT in the PFC and ACC (MANOVA, severity: F(2,38)=5.44, p=0.008; reversed neurovegetative symptoms: F(2,38)=5.13, p=0.01). Increased MAO-A level, when greater severity and reversed neurovegetative symptoms are present, may explain the association of these clinical features with a preferential response to MAO inhibitors, which is especially well-evidenced for reversed neurovegetative symptoms in MDE. As MAO-A creates oxidative stress, facilitates apoptosis, and metabolizes monoamines, therapeutics opposing these processes are predicted to best treat MDE with greater severity and reversed neurovegetative symptoms.
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PMID:Elevated monoamine oxidase a binding during major depressive episodes is associated with greater severity and reversed neurovegetative symptoms. 2415 65

There are a number of neurocognitive and behavioral mechanisms that contribute to overeating and obesity, including an attentional bias to food cues. Attention modification programs, which implicitly train attention away from specific cues, have been used in anxiety and substance abuse, and could logically be applied to food cues. The purpose of this study was to evaluate the initial efficacy of a single session attention modification training for food cues (AMP) on overeating in overweight and obese children. Twenty-four obese children who eat in the absence of hunger participated in two visits and were assigned to an attention modification program (AMP) or attentional control program (ACC). The AMP program trained attention away 100% of the time from food words to neutral words. The ACC program trained attention 50% of the time to neutral and 50% of the time to food. Outcome measures included the eating in the absence of hunger free access session, and measures of craving, liking and salivation. Results revealed significant treatment effects for EAH percent and EAH kcal (group by time interactions p<.05). Children in the ACC condition showed a significant increase over time in the number of calories consumed in the free access session (within group t=3.09, p=.009) as well as the percent of daily caloric needs consumed in free access (within group t=3.37, p=.006), whereas children in the AMP group demonstrated slight decreases in these variables (within group t=-0.75 and -0.63, respectively). There was a trend suggesting a beneficial effect of AMP as compared to ACC for attentional bias (group by time interaction p=.073). Changes in craving, liking and saliva were not significantly different between groups (ps=.178-.527). This is the first study to demonstrate that an AMP program can influence eating in obese children. Larger studies are needed to replicate and extend these results.
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PMID:A pilot study evaluating a one-session attention modification training to decrease overeating in obese children. 2451 75