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

Increased albuminuria is associated with obesity and diabetes and is a risk factor for cardiovascular and renal disease. However, the link between early albuminuria and adiposity remains unclear. To determine whether adiponectin, an adipocyte-derived hormone, is a communication signal between adipocytes and the kidney, we performed studies in a cohort of patients at high risk for diabetes and kidney disease as well as in adiponectin-knockout (Ad(-/-)) mice. Albuminuria had a negative correlation with plasma adiponectin in obese patients, and Ad(-/-) mice exhibited increased albuminuria and fusion of podocyte foot processes. In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane. These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes. Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress. These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.
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PMID:Adiponectin regulates albuminuria and podocyte function in mice. 1843 7

Detailed knowledge of the pathways by which ghrelin and leptin signal to AMPK in hypothalamic neurons and lead to regulation of appetite and glucose homeostasis is central to the development of effective means to combat obesity. Here we identify CaMKK2 as a component of one of these pathways, show that it regulates hypothalamic production of the orexigenic hormone NPY, provide evidence that it functions as an AMPKalpha kinase in the hypothalamus, and demonstrate that it forms a unique signaling complex with AMPKalpha and beta. Acute pharmacologic inhibition of CaMKK2 in wild-type mice, but not CaMKK2 null mice, inhibits appetite and promotes weight loss consistent with decreased NPY and AgRP mRNAs. Moreover, the loss of CaMKK2 protects mice from high-fat diet-induced obesity, insulin resistance, and glucose intolerance. These data underscore the potential of targeting CaMKK2 as a therapeutic intervention.
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PMID:Hypothalamic CaMKK2 contributes to the regulation of energy balance. 1846 Mar 26

In management of metabolic syndrome, the traditional Chinese medicine (TCM) is an excellent representative in alternative and complementary medicines with a complete theory system and substantial herb remedies. In this article, basic principle of TCM is introduced and 25 traditional Chinese herbs are reviewed for their potential activities in the treatment of metabolic syndrome. Three herbs, ginseng, rhizoma coptidis (berberine, the major active compound) and bitter melon, were discussed in detail on their therapeutic potentials. Ginseng extracts made from root, rootlet, berry and leaf of Panax quinquefolium (American ginseng) and Panax ginseng (Asian ginseng), are proved for anti-hyperglycemia, insulin sensitization, islet protection, anti-obesity and anti-oxidation in many model systems. Energy expenditure is enhanced by ginseng through thermogenesis. Ginseng-specific saponins (ginsenosides) are considered as the major bioactive compounds for the metabolic activities of ginseng. Berberine from rhizoma coptidis is an oral hypoglycemic agent. It also has anti-obesity and anti-dyslipidemia activities. The action mechanism is related to inhibition of mitochondrial function, stimulation of glycolysis, activation of AMPK pathway, suppression of adipogenesis and induction of low-density lipoprotein (LDL) receptor expression. Bitter melon or bitter gourd (Momordica charantia) is able to reduce blood glucose and lipids in both normal and diabetic animals. It may also protect beta cells, enhance insulin sensitivity and reduce oxidative stress. Although evidence from animals and humans supports the therapeutic activities of ginseng, berberine and bitter melon, multi-center large-scale clinical trials have not been conducted to evaluate the efficacy and safety of these herbal medicines.
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PMID:Traditional chinese medicine in treatment of metabolic syndrome. 1853 96

The aim of this study was to investigate the chronic effects of palmitate on fatty acid (FA) oxidation, AMPK/ACC phosphorylation/activation, intracellular lipid accumulation, and the molecular mechanisms involved in these processes in skeletal muscle cells. Exposure of L6 myotubes for 8 h to 200, 400, 600, and 800 microM of palmitate did not affect cell viability but significantly reduced FA oxidation by approximately 26.5%, approximately 43.5%, approximately 50%, and approximately 47%, respectively. Interestingly, this occurred despite significant increases in AMPK ( approximately 2.5-fold) and ACC ( approximately 3-fold) phosphorylation and in malonyl-CoA decarboxylase activity ( approximately 38-60%). Low concentrations of palmitate (50-100 microM) caused an increase ( approximately 30%) in CPT-1 activity. However, as the concentration of palmitate increased, CPT-1 activity decreased by approximately 32% after exposure for 8 h to 800 microM of palmitate. Although FA uptake was reduced ( approximately 35%) in cells exposed to increasing palmitate concentrations, intracellular lipid accumulation increased in a dose-dependent manner, reaching values approximately 2.3-, approximately 3-, and 4-fold higher than control in muscle cells exposed to 400, 600, and 800 microM palmitate, respectively. Interestingly, myotubes exposed to 400 microM of palmitate for 1 h increased basal glucose uptake and glycogen synthesis by approximately 40%. However, as time of incubation in the presence of palmitate progressed from 1 to 8 h, these increases were abolished and a time-dependent inhibition of insulin-stimulated glucose uptake ( approximately 65%) and glycogen synthesis ( approximately 30%) was observed in myotubes. These findings may help explain the dysfunctional adaptations that occur in glucose and FA metabolism in skeletal muscle under conditions of chronically elevated circulating levels of non-esterified FAs, such as in obesity and Type 2 Diabetes.
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PMID:Prolonged exposure to palmitate impairs fatty acid oxidation despite activation of AMP-activated protein kinase in skeletal muscle cells. 1856 Dec 58

The causal relationship between obesity and cardiovascular disease is extensively acknowledged; however, the exact mechanisms linking obesity and heart failure remain unclear. Here, we investigated the influence of adipokines derived from primary adipocytes on glucose and fatty acid uptake and metabolism in isolated primary cardiomyocytes. Either co-culture of these cell types or incubation with adipocyte-conditioned medium significantly increased glucose uptake in cardiomyocytes. When streptozotocin-induced diabetic rats were used as a source of adipocytes, there was a lower ability to elicit glucose uptake in cardiomyocytes which corresponded with lower Akt and AMPK phosphorylation. The profile of glucose metabolism also differed with oxidation being favored upon co-culture with wild-type adipocytes whereas lactate production was strongly induced by adipocytes from diabetic rats. Examination of fatty acid uptake revealed that stimulation only occurred in response to adipokines secreted by wild-type rat adipocytes. Importantly, oxidation of fatty acids by cardiomyocytes was decreased by adipokines derived from diabetic rat adipocytes. Analysis of adipokine profiles in diabetic rat adipocyte-conditioned medium demonstrated the most significant decreases in adiponectin and leptin with increased IL6 expression. Taken together, these data suggest that the profile of adipokines secreted by adipocytes from diabetic rats have a deleterious influence on cardiomyocyte metabolism which may be of relevance in the pathophysiology of heart failure.
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PMID:Differential impact of adipokines derived from primary adipocytes of wild-type versus streptozotocin-induced diabetic rats on glucose and fatty acid metabolism in cardiomyocytes. 1878 59

Chronic kidney disease (CKD) in ageing is a burden on health systems worldwide. Rat models of age-related CKD linked with obesity and hypertension were used to investigate alterations in oxidant handling and energy metabolism to identify gene targets or markers for age-related CKD. Young adult (3 months) and old (21-24 months) spontaneously-hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar rats (normotensive, obese in ageing) were compared for renal functional and physiological parameters, renal fibrosis and inflammation, oxidative stress (hemeoxygenase-1/HO-1), apoptosis and cell injury (including Bax:Bcl-2), phosphorylated and non-phosphorylated forms of oxidant and energy sensing proteins (p66Shc, AMPK), signal transduction proteins (ERK1/2, PKB), and transcription factors (NF-kappaB, FoxO1). All old rats were normoglycemic. Renal fibrosis, tubular epithelial apoptosis, interstitial macrophages and myofibroblasts (all p<0.05), p66Shc/phospho-p66 (p<0.05), Bax/Bcl-2 ratio (p<0.05) and NF-kappaB expression (p<0.01) were highest in old obese Wistars. Expression of phospho-FoxO/FoxO was elevated in old Wistars (p<0.001) and WKYs (p<0.01). SHRs had high levels in young and old rats. Expression of PKB, phospho-PKB, ERK1/2 and phospho-ERK1/2 were significantly elevated in all aged animals. These results suggest that obesity and hypertension have differing oxidant handling and signalling pathways that act in the pathogenesis of age-related CKD.
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PMID:Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease. 1904 34

The NAD(+)-dependent deacetylase SIRT1 controls metabolic processes in response to low nutrient availability. We report the metabolic phenotype of mice treated with SRT1720, a specific and potent synthetic activator of SIRT1 that is devoid of direct action on AMPK. SRT1720 administration robustly enhances endurance running performance and strongly protects from diet-induced obesity and insulin resistance by enhancing oxidative metabolism in skeletal muscle, liver, and brown adipose tissue. These metabolic effects of SRT1720 are mediated by the induction of a genetic network controlling fatty acid oxidation through a multifaceted mechanism that involves the direct deacetylation of PGC-1alpha, FOXO1, and p53 and the indirect stimulation of AMPK signaling through a global metabolic adaptation mimicking low energy levels. Combined with our previous work on resveratrol, the current study further validates SIRT1 as a target for the treatment of metabolic disorders and characterizes the mechanisms underlying the therapeutic potential of SIRT1 activation.
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PMID:Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. 1904 67

Obesity is one of the most prevalent medical conditions, often associated with several negative stereotypes. Although it is true that weight gain occurs when food intake exceeds energy expenditure, it is important to note that even a 1% mismatch between the two can lead to a substantial weight gain after only a few years. Further, the body appears to balance energy metabolism via an endogenous lipostatic loop in which adipose stores send hormonal signals (e.g. adipokines such as leptin) to the hypothalamus in order to reduce appetite and increase energy expenditure. However, the brain is also a novel site of expression of many of these adipokine genes. This led to the hypothesis that hypothalamic-derived adipokines might also be involved in bodyweight regulation by exerting some effect on the control of appetite or hypothalamic function. When RNA interference (RNAi) was used to specifically silence adipokine gene expression in various in vitro models, this led to increases in cell death, modification of the expression of key signaling genes (i.e. suppressor of cytokine signaling-3; SOCS-3), and modulation of the activation of cellular energy sensors (i.e. adenosine monophosphate-activated protein kinase; AMPK). Subsequently, when RNAi was used to inhibit the expression of brain-derived leptin in adult rats this resulted in minor increases in weight gain in addition to modifying the expression of other adipokine genes (eg. resistin). In summary, although adipokines secreted by adipose tissue appear to the main regulator of lipostatic loop, this review shows that the fine tuning that is required to maintain a stable bodyweight by this system might be accomplished by hypothalamic-derived adipokines. Perturbations in this central adipokine system could lead to alterations in normal hypothalamic function which leads to unintended weight gain.
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PMID:Could there be a fine-tuning role for brain-derived adipokines in the regulation of bodyweight and prevention of obesity? 1914 19

Omega-3-polyunsaturated fatty acids (omega-3-PUFAs) have well-documented protective effects that are attributed not only to eicosanoid inhibition but also to the formation of novel biologically active lipid mediators (i.e., resolvins and protectins). In this study, we examined their effects on ob/ob mice, an obesity model of insulin resistance and fatty liver disease. Dietary intake of omega-3-PUFAs had insulin-sensitizing actions in adipose tissue and liver and improved insulin tolerance in obese mice. Genes involved in insulin sensitivity (PPARgamma), glucose transport (GLUT-2/GLUT-4), and insulin receptor signaling (IRS-1/IRS-2) were up-regulated by omega-3-PUFAs. Moreover, omega-3-PUFAs increased adiponectin, an anti-inflammatory and insulin-sensitizing adipokine, and induced AMPK phosphorylation, a fuel-sensing enzyme and a gatekeeper of the energy balance. Concomitantly, hepatic steatosis was alleviated by omega-3-PUFAs. A lipidomic analysis with liquid chromatography/mass spectrometry/mass spectrometry revealed that omega-3-PUFAs inhibited the formation of omega-6-PUFA-derived eicosanoids, while triggering the formation of omega-3-PUFA-derived resolvins and protectins. Moreover, representative members of these lipid mediators, namely resolvin E1 and protectin D1, mimicked the insulin-sensitizing and antisteatotic effects of omega-3-PUFAs and induced adiponectin expression to a similar extent that of rosiglitazone, a member of the thiazolidinedione family of antidiabetic drugs. Taken together, these findings uncover beneficial actions of omega-3-PUFAs and their bioactive lipid autacoids in preventing obesity-induced insulin resistance and hepatic steatosis.
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PMID:Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. 1921 25

When interrogating the activation status of AMP-activated protein kinase-measured as AMPKalpha(Thr172) phosphorylation-in tissue sections of human carcinomas and in cultured human cancer cells, the spatiotemporal dynamics of AMPK activity during the G(1)/S-to-M-phase transition strikingly resembles that of well-characterized "chromosomal passenger" proteins such as Aurora B, INCENP or Histone H3. The mitotic kinase behavior of the active form of AMPK may represent a candidate molecular link through which energy status directly influences tumorigenesis. A definitive elucidation of phospho-AMPKalpha(Thr172) in coordinating the chromosomal and cytoskeletal events of mitosis might radically amend our current perception of other AMPK-related diseases such as obesity, cardiac hypertrophy or accelerated aging syndromes.
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PMID:Mitotic kinase dynamics of the active form of AMPK (phospho-AMPKalphaThr172) in human cancer cells. 1922 86


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