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

The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial. Using in vitro cell culture models, we show that n-6 PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti-adipogenic when the levels of cAMP were elevated. The anti-adipogenic action of n-6 PUFAs was dependent on a cAMP-dependent protein kinase-mediated induction of cyclooxygenase expression and activity. We show that n-6 PUFAs were pro-adipogenic when combined with a high carbohydrate diet, but non-adipogenic when combined with a high protein diet in mice. The high protein diet increased the glucagon/insulin ratio, leading to elevated cAMP-dependent signaling and induction of cyclooxygenase-mediated prostaglandin synthesis. Mice fed the high protein diet had a markedly lower feed efficiency than mice fed the high carbohydrate diet. Yet, oxygen consumption and apparent heat production were similar. Mice on a high protein diet had increased hepatic expression of PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha) and genes involved in energy-demanding processes like urea synthesis and gluconeogenesis. We conclude that cAMP signaling is pivotal in regulating the adipogenic effect of n-6 PUFAs and that diet-induced differences in cAMP levels may explain the ability of n-6 PUFAs to either enhance or counteract adipogenesis and obesity.
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PMID:cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids. 1807 Aug 79

After the CB1 receptor antagonist SR141716 (rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. Several series of urea, carbamate, amide, sulfonamide and oxalamide derivatives based on 1-benzhydrylpiperazine scaffold were synthesized and tested for CB1 receptor binding affinity. The SAR studies to optimize the CB1 binding affinity led to the potent urea derivatives. After the additional SAR studies to optimize the substituents of diphenyl rings, the combination of 2-chlorophenyl and 4-chlorophenyl turned out to be the most potent scaffold. The CB2 binding affinity assay as well as functional assay was also conducted on these compounds. Herein we wish to introduce several novel CB1 antagonists with IC(50) values less than 100 nM for the CB1 receptor binding.
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PMID:Design, synthesis and biological evaluation of piperazine analogues as CB1 cannabinoid receptor ligands. 1824 11

The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. The SDT-fa/fa (SDT fatty) rat shows overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with the SDT-+/+ (SDT normal) rat. However, the features of the diabetic complications in the SDT fatty rat have not been reported. In the present study, the incidence and the progression of diabetic complications in the SDT fatty rat were examined, and compared with those of the SDT normal rat. Renal function parameters, such as blood urea nitrogen, urine volume and urinary protein, increased from 4 weeks of age in the SDT fatty rat, and pathological findings in the renal tubule were observed from 8 weeks. Furthermore, cataract was observed in the SDT fatty rat from 8 weeks of age, and prolongation of peak latencies on electroretinograms was observed at 16 and 24 weeks of age. On the other hand, in the SDT normal rat, renal or ocular changes were observed from 24 weeks of age. With early incidence of diabetes mellitus, diabetes-associated complications in the SDT fatty rat were seen at younger ages than those in the SDT normal rat. In conclusion, the SDT fatty rat is expected to be a useful model for the analysis of diabetic complications and the evaluation of drugs related to metabolic diseases.
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PMID:Diabetes-associated complications in Spontaneously Diabetic Torii fatty rats. 1842 Nov 73

A 56-year-old woman with obesity and poorly controlled diabetes mellitus presented with a two-day history of abdominal fullness and vomiting. No fever, flank pain or dysuria was present. On admission, her blood urea nitrogen concentration was 74 mg per deciliter and the serum creatinine concentration was 3.5 mg per deciliter. Laboratory data revealed an elevated white blood cell count (11.72 x 10(3)/ml), blood sugar (826 mg/dl), pyuria (WBC 30-50/HPF) and negative urine ketone. A plain abdominal radiograph revealed right renal stones and localized air accumulation at the left upper abdominal area.
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PMID:Emphysematous pyelonephritis with acute renal failure. 1861 55

Childhood obesity is an increasingly serious problem; 13.9 percent of children two to five years of age, 18.8 percent of children six to 11 years of age, and 17.4 percent of adolescents 12 to 19 years of age in America are obese. Practical strategies that primary care physicians can use to tackle the problem are scarce. The American Medical Association recently convened an expert panel to address this need. Evidence about how best to manage and prevent obesity was reviewed and incorporated into a series of reports. The Expert Committee on the Assessment, Prevention, and Treatment of Child and Adolescent Overweight and Obesity recommends addressing the issue of weight with all children at least once a year. Family physicians are urged to assess key dietary habits (e.g., consumption of sweetened beverages), physical activity habits, readiness to change lifestyle habits, and family history of obesity and obesity-related illnesses. Laboratory testing recommendations depend on the degree of obesity and associated illnesses. For children with a body mass index between the 85th and 94th percentiles but who have no obesity-related illnesses, a fasting lipid profile should be done. Those with the same body mass index and obesity-related illnesses should also have tests for alanine transaminase, aspartate transaminase, and fasting blood glucose levels. Measurement of blood urea nitrogen and creatinine levels should be added in children with a body mass index above the 95th percentile. A four-stage approach to treatment of childhood obesity is recommended. Many of these recommendations can be carried out by family physicians for treatment and prevention. These include advising families to limit consumption of sweetened beverages and fast food, limit screen time, engage in physical activity for at least 60 minutes per day, and encourage family meals on most, and preferably all, days of the week.
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PMID:Childhood obesity: highlights of AMA Expert Committee recommendations. 1864 8

Resistin, a small secreted peptide initially identified as a link between obesity and diabetes in mice, was shown to be involved in mediating inflammation in humans. We had shown earlier that recombinant human resistin has a tendency to form aggregates by formation of inter/intramolecular disulfide linkages and that it undergoes a concentration-dependent conformational change in secondary structure from alpha-helical to beta-sheet form. Here we report that this change in secondary structural conformation is due to the increase in the oligomeric form of human resistin as a function of protein concentration. Gel filtration analysis under different conditions further demonstrated that recombinant human resistin exists as a mixture of oligomer and trimer but is converted to a mixture of monomer and oligomer in the presence of 100 mM NaCl. We show that while the trimeric form of human resistin is stable to urea-induced denaturation, it is highly susceptible to NaCl and NaF, indicating the importance of ionic interactions in stabilization of trimer. In addition, urea was able to destabilize the oligomers indicating the involvement of hydrophobic interactions in oligomerization. Ionic as well as hydrophobic interactions stabilize the monomeric human resistin. Our data suggest that human resistin exists predominantly as oligomer and trimer in vitro. The oligomeric form of human resistin shows more potent effect on stimulation of proinflammatory cytokines. Therefore, it is very tempting to propose that the structural conformation of resistin may be involved in maintaining the very fine balance in regulation of macrophage function for successful response to a variety of pathological conditions.
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PMID:Biophysical analyses of human resistin: oligomer formation suggests novel biological function. 1897 14

The neuropeptide Y (NPY) Y(5) receptor is believed to be involved in the central regulation of appetite. Thus, antagonists of this receptor have been pursued as potential therapeutic agents for the treatment of obesity. A novel series of potent and selective phenylamide or biaryl urea NPY Y(5) receptor antagonists was identified. Four representative compounds from this series, SCH 208639 (N-[4-[(1,1-dimethylbutyl)thio]phenyl]-2,2-dimethylpropanamide), SCH 430765 (N-[[[3'-fluoro[1,1'-biphenyl]-4-yl]amino]carbonyl]-N-methyl-1-(methylsulfonyl)-4-piperidinamine), SCH 488106 (N-[[[3',5'-difluoro[1,1'-biphenyl]-4-yl]amino]carbonyl]-N-methyl-1-[(5-methyl-3-pyridinyl)carbonyl]-4-piperidinamine) and SCH 500946 (N-[[[5-(3,5-difluorophenyl)-2-pyrazinyl]amino]carbonyl]-N-methyl-1-(methylsulfonyl)-4-piperidinamine), behaved as competitive antagonists in radioligand binding assays, but displayed apparently insurmountable antagonism in a cell-based functional assay. The apparently insurmountable antagonism was due to slow receptor dissociation rates rather than covalent binding, because the antagonists' effects could be reduced by extensive washing of cells after antagonist exposure. A novel radioligand, [(35)S]SCH 500946, was also developed and used to characterize the interaction of these antagonists with the NPY Y(5) receptor. [(35)S]SCH 500946 had high affinity for the NPY Y(5) receptor (K(d)=0.29 nM), and the binding kinetics (k(on) 4.414 x 10(7) M(-)(1) min(-1); k(off) 0.009816 min(-1)) confirmed that the compound slowly dissociates from the receptor. In a competition binding assay, NPY failed to displace [(35)S]SCH 500946 completely, indicating that the binding sites for NPY and [(35)S]SCH 500946 are not identical. These data indicate that the apparent insurmountable antagonism of these NPY Y(5) receptor antagonists is attributable both to slow receptor dissociation rates and to binding at a site distinct from NPY.
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PMID:Identification and characterization of pseudoirreversible nonpeptide antagonists of the neuropeptide Y Y5 receptor and development of a novel Y5-selective radioligand. 1897 48

Acute pancreatitis is a dynamic, often progressive disease; 14-20% require intensive care in its severe form due to multiorgan dysfunction and/or failure. This review was created using systematic literature review of articles published on this subject in the last 5 years. The outcome of severe acute pancreatitis is determined by the inflammatory response and multiorgan dysfunction - the prognostic scores (Acute Physiology and Chronic Health Evaluation, Glasgow Prognostic Index, Sepsis-related Organ Failure Assessment, Multi Organ Dysfunction Syndrome Scale, Ranson Scale) can be used to determine outcome. Clinical signs (age, coexisting diseases, confusion, obesity) and biochemistry values (serum amylase, lipase, C-reactive protein, procalcitonin, creatinine, urea, calcium) have important prognostic roles as well. Early organ failure increases the risk of late abdominal complications and mortality. Intensive care can provide appropriate multi-function patient monitoring which helps in early recognition of complications and appropriate target-controlled treatment. Treatment of severe acute pancreatitis aims at reducing systemic inflammatory response and multiorgan dysfunction and, on the other side, at increasing the anti-inflammatory response. Oral starvation for 24-48 hours is effective in reducing the exocrine activity of the pancreas; the efficacy of protease inhibitors is questionable. Early intravascular volume resuscitation and stable haemodynamics improve microcirculation. Early oxygen therapy and mechanical ventilation provide adequate oxygenation. Electrolyte and acid-base control can be as important as tight glucose control. Adequate pain relief can be achieved by thoracic epidural catheterization. Early enteral nutrition with immunonutrition should be used. There is evidence that affecting the coagulation cascade by activated protein C can play a role in reducing the inflammatory response. The complex therapy of acute pancreatitis includes appropriate antibiotics, thrombo-embolic prophylaxis and in certain cases plasmapheresis and/or haemofiltration. Reducing intraabdominal pressure may be necessary in the acute phase. Intensive care multidisciplinary teamwork can reduce the mortality of severe acute pancreatitis from 30% to 10%.
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PMID:[Principles of intensive care in severe acute pancreatitis in 2008]. 1900 43

Previous studies showed that dietary L-arginine supplementation decreased white fat mass in genetically obese rats. This study tested the effectiveness of L-arginine in diet-induced obesity. Male Sprague-Dawley rats were fed for 15 wk a high-fat (HF) (40% energy) or low-fat (LF) (10% energy) diet beginning at 4 wk of age, resulting in 18% higher body weight gains and 74% higher weights of major white fat pads (retroperitoneal, epididymal, subcutaneous, and mesenteric adipose tissues) in HF than in LF fed rats. Starting at 19 wk of age, rats in each dietary group were supplemented for 12 wk with 1.51% L-arginine-HCl or 2.55% L-alanine (isonitrogenous control) (n = 8 per treatment) in drinking water and arginine groups were individually pair-fed to alanine controls. Despite similar energy intake, absolute weights of white fat pads increased by 98% in control rats over a 12-wk period but only by 35% in arginine-supplemented rats. The arginine treatment reduced the relative weights of white fat pads by 30% and enhanced those of soleus muscle by 13%, extensor digitorum longus muscle by 11%, and brown fat by 34% compared with control rats. Serum concentrations of insulin, adiponectin, growth hormone, corticosterone, triiodothyronine, and thyroxine did not differ between control and arginine-supplemented rats. However, arginine treatment resulted in lower serum concentrations of leptin, glucose, triglycerides, urea, glutamine, and branched-chain amino acids, higher serum concentrations of nitric-oxide metabolites, and improvement in glucose tolerance. Thus, dietary arginine supplementation shifts nutrient partitioning to promote muscle over fat gain and may provide a useful treatment for improving the metabolic profile and reducing body white fat in diet-induced obese rats.
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PMID:Dietary L-arginine supplementation reduces white fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats. 1910 10

The role of dietary protein in weight loss and weight maintenance encompasses influences on crucial targets for body weight regulation, namely satiety, thermogenesis, energy efficiency, and body composition. Protein-induced satiety may be mainly due to oxidation of amino acids fed in excess, especially in diets with "incomplete" proteins. Protein-induced energy expenditure may be due to protein and urea synthesis and to gluconeogenesis; "complete" proteins having all essential amino acids show larger increases in energy expenditure than do lower-quality proteins. With respect to adverse effects, no protein-induced effects are observed on net bone balance or on calcium balance in young adults and elderly persons. Dietary protein even increases bone mineral mass and reduces incidence of osteoporotic fracture. During weight loss, nitrogen intake positively affects calcium balance and consequent preservation of bone mineral content. Sulphur-containing amino acids cause a blood pressure-raising effect by loss of nephron mass. Subjects with obesity, metabolic syndrome, and type 2 diabetes are particularly susceptible groups. This review provides an overview of how sustaining absolute protein intake affects metabolic targets for weight loss and weight maintenance during negative energy balance, i.e., sustaining satiety and energy expenditure and sparing fat-free mass, resulting in energy inefficiency. However, the long-term relationship between net protein synthesis and sparing fat-free mass remains to be elucidated.
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PMID:Dietary protein, weight loss, and weight maintenance. 1940 Jul 50


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