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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The organizing power of energy flow is hypothesized to be the origin of biological complexity and its decline the basis of "complex" diseases and aging. Energy flow through organic systems creates nucleic acids, which store information, and the annual accumulation of information generates today's complexity. Energy flow through our bodies is mediated by the mitochondria, symbiotic bacteria whose genomes encompass the mitochondrial DNA (mtDNA) and more than 1000 nuclear genes. Inherited and/or epigenomic variation of the mitochondrial genome determines our initial energetic capacity, but the age-related accumulation of somatic cell mtDNA mutations further erodes energy flow, leading to disease. This bioenergetic perspective on disease provides a unifying pathophysiological and genetic mechanism for neuropsychiatric diseases such as Alzheimer and Parkinson Disease, metabolic diseases such as diabetes and obesity, autoimmune diseases, aging, and cancer.
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PMID:Bioenergetic origins of complexity and disease. 2219 59

Sequestosome 1/p62 is a signal modulator or adaptor protein involved in receptor-mediated signal transduction. Sequestosome 1/p62 is gaining attention as it is involved in several diseases including Parkinson disease, Alzheimer disease, liver and breast cancer, Paget's disease of bone, obesity and insulin resistance. In this review, we will focus on the most recent advances on the physiological function of p62 relevant to human diseases.
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PMID:Sequestosome 1/p62: across diseases. 2229 16

Inflammation is part of the innate immune response following insults to the body. This inflammatory reaction can spread throughout the systemic circulation and also into the central nervous system (CNS). CNS involvement has been demonstrated following acute peripheral insults including sepsis, surgery, burns and organ injury. It has also been observed in chronic conditions including obesity, diabetes and rheumatoid arthritis. Inflammation within the CNS is part of the pathogenesis of neurodegenerative diseases, in particular Alzheimer's disease, multiple sclerosis and Parkinson's disease. These diseases are prone to exacerbation as a result of increased inflammation within the CNS following peripheral insult. The effect of inflammation within the CNS can also be modulated by other factors including age and also oestrogen, although how pro-inflammatory cytokines within the CNS cause clinical changes remains to be elucidated. The mechanism underlying the passage of inflammation from the periphery into the CNS also remains unclear. Evidence has led to the suggestion of two main pathways: blood brain barrier (BBB) dependent and BBB independent. This uncertainty has led to an increasing body of work exploring the processes involved in both the passage of inflammation into, and the effect of cytokines on, the CNS.
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PMID:Central nervous system inflammation in disease related conditions: mechanistic prospects. 2234 62

High-frequency deep brain stimulation (HF-DBS) has become a widely used therapeutic method in the field of movement disorders for the treatment of Parkinson's disease, essential tremor or dystonia. New targets and indications are under evaluation in several other conditions such as cluster headache, obesity, epilepsy or psychiatric diseases (depression, OCD). However, the mechanisms of action of HF-DBS remain poorly understood. Herein we present a review of the literature and our current view of the question. The first part deals with the effects of stimulation itself on the different parts of the neuron and tries to answer the question of what is actually stimulated by DBS (cell bodies, dendrites or axons). The second part is devoted to the ortho- and antidromic effects of the stimulation. The third part more specifically focuses on the case of subthalamic nucleus stimulation. The target axons in the subthalamic area are discussed in the light of recent optogenetic studies. In conclusion, HF-DBS leads to a kind of functional deafferentation of the stimulated structure and to the modulation of cortical activity (both ortho and antidromically). Which effects are relevant to the therapeutic effects of DBS is still unclear. Further investigations are required especially regarding the corticosubthalamic pathways.
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PMID:[Mechanisms of action of high-frequency deep brain stimulation. A review of the literature and current concepts]. 2246 40

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two debilitating health disorders afflicting millions worldwide. Recent research has revealed similarities between AD and T2DM. Both these protein conformational disorders are associated with obesity, insulin resistance, inflammation and endoplasmic reticulum stress, en-route initiation and/or stage aggravation. In this mini review we have tried to summarize studies describing obesity, insulin resistance and glucocorticoid imbalance as common patho-mechanisms in T2DM and AD. A reduction in tyrosine hydroxylase (TH) in the brain has been found to occur in Parkinson's disease (PD). AD, T2DM and PD share common risk factors like depression. Thus, whether TH is involved in the 'state of cognitive depression' that is the hallmark of AD and often accompanies PD and T2DM is also explored.
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PMID:Alzheimer's disease and type 2 diabetes: exploring the association to obesity and tyrosine hydroxylase. 2258 31

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. To date, genetic causes and underlying molecular mechanisms for sporadic PD remain largely unknown. Sirtuis are highly conserved NAD-dependent class III deacetylases. SIRT1, the closest to yeast Sir2, has deacetylase activity and ADP-ribosyltransferase activity. SIRT1 gene has been connected to many cellular processes and implicated in human diseases, such as obesity, type 2 diabetes, cancer and neurodegenerative diseases. Studies in animal model have also associated SIRT1 with aggregation of alpha-synuclein, a critical protein in the PD pathogenesis. We hypothesized that the genetic variants within the regulatory regions of SIRT1 gene that repress its gene expression, rather than mutations in its coding region that abolish SIRT1 function, may contribute to PD as a risk factor. In this study, we genetically analyzed the promoter region of SIRT1 gene in sporadic PD patients and ethic-matched healthy controls. Three novel heterozygous sequence variants, g.69644133C>G, g.69644213G>A and g.69644351G>A, were identified in PD patients, but in none of controls, which may alter the transcriptional activities of SIRT1 gene promoter, resulting in reduced SIRT1 levels. One novel heterozygous variant, g.69644219G>A, linked with single-nucleotide polymorphism - g.69644217A>C (rs932658), was only found in one control, which may have no functional activity. Therefore, our results suggested that genetic variants within the SIRT1 gene promoter may repress SIRT1 gene expression, contributing to PD as a risk factor.
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PMID:Genetic analysis of SIRT1 gene promoter in sporadic Parkinson's disease. 2261 5

Changes in the nutritional profile of patients with Parkinson's disease have been reported before and after deep brain stimulation surgery. The major determinants of the weight variation in Parkinson's disease are not yet understood, and the mechanism seems complex. Based on the influence of the sympathetic nervous system in metabolic syndrome obesity, the intent of the present review is to consider the role of noradrenergic modulation on weight variations in Parkinson's disease. In this review the authors raise the following hypothesis: weight variation in Parkinson's disease before and after deep brain stimulation of the subthalamic nucleus could be influenced by noradrenergic interaction between the locus coeruleus, subthalamic nucleus, and hypothalamic nucleus.
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PMID:Weight variation before and after surgery in Parkinson's disease: a noradrenergic modulation? 2270 Mar 83

Helicobacter pylori (H. pylori) infection is reported to be associated with many extragastrointestinal manifestations, such as hematological diseases [idiopathic thrombocytopenic purpura (ITP) and unexplained iron deficiency anemia (IDA)], cardiovascular diseases (ischemic heart diseases), neurological disorders (stroke, Parkinson's disease, Alzheimer's disease), obesity and skin disorders. Among these, the best evidence so far is in ITP and unexplained IDA, with high-quality studies showing the improvement of IDA and ITP after H. pylori eradication. The evidence of its association with coronary artery disease is weak and many of the results may be erroneous. The role of H. pylori infection in affecting serum leptin and ghrelin levels has attracted a lot of attention recently and available data to date have been conflicting. There have also been many uncontrolled, small sample studies suggesting an association between H. pylori infection and neurological disorders or chronic urticaria. However, more studies are required to clarify such proposed causal links.
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PMID:Extragastrointestinal manifestations of Helicobacter pylori infection: facts or myth? A critical review. 2271 83

Resistin is originally reported as an adipose tissue-specific hormone and is thought to represent a link between obesity and insulin-resistant diabetes. Adipokines exert energy-regulation and has been reported to have neuroprotective effect like leptin, adiponectin, and ghrelin. However, the role of resistin in neuroprotective effect has not been explored. 6-hydroxydopamine (6-OHDA), one of the most investigated Parkinson's disease neurotoxins, is widely used to study mechanisms of cell death in dopaminergic neurons. In the present study, our results show that treatment of resistin protects 6-OHDA-induced cell death in dopaminergic-like MES23.5 cells. Resistin also antagonizes 6-OHDA-induced apoptotic cell death measured by fluorescence-activated cell sorter (FACS) analysis and Hochest 33342 staining. Furthermore, treatment of resistin also dramatically reduces 6-OHDA-mediated ROS production and mitochondria transmembrane potential dissipation. Moreover, expression of 6-OHDA-induced apoptotic markers, such as Bcl-2 degradation, Bax expression, PARP degradation and caspase 3 activity increase, are all attenuated by resistin treatment. Our results also show that resistin induces up-regulation of heat shock protein (Hsp) 32 (heme oxygenase-1, HO-1) and Hsc (heat shock cognate) 70. The protective effect of resistin on 6-OHDA-induced cell death is abolished by HO-1 inhibitor zinc protoporphyrin IX and HSP inhibitor KNK437. These results suggest the neuroprotective effects of resistin against 6-OHDA-induced cell death with the underlying mechanisms of inhibiting oxidative stress and apoptosis. Therefore, we suggest that resistin may provide a useful therapeutic strategy for neurodegenerative diseases such as Parkinson's disease.
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PMID:Resistin protects against 6-hydroxydopamine-induced cell death in dopaminergic-like MES23.5 cells. 2280 54

The success of deep brain stimulation (DBS) surgery in treating medically refractory symptoms of some movement disorders has inspired further investigation into a wide variety of other treatment-resistant conditions. These range from disorders of gait, mood, and memory to problems as diverse as obesity, consciousness, and addiction. We review the emerging indications, rationale, and outcomes for some of the most promising new applications of DBS in the treatment of postural instability associated with Parkinson's disease, depression, obsessive-compulsive disorder, obesity, substance abuse, epilepsy, Alzheimer's-type dementia, and traumatic brain injury. These studies reveal some of the excitement in a field at the edge of a rapidly expanding frontier. Much work still remains to be done on basic mechanism of DBS, optimal target and patient selection, and long-term durability of this technology in treating new indications.
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PMID:Novel applications of deep brain stimulation. 2282 7


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