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

The influence of dietary composition on whole-body energetics was examined during the first 2 weeks of isocaloric refeeding after low food intake in a rat model. The high energetic efficiency and energy partitioning toward fat accretion characteristic of this refeeding period were unaltered by (1) dietary fat levels varying between 6% and 30% of energy intake; (2) protein levels between 15% and 40%; (3) carbohydrate types (glucose v fructose v sucrose v starch v unrefined carbohydrate); and (4) diets containing 30% fat but differing in fatty acid composition (long-chain triglycerides [LCT] v medium-chain triglycerides [MCT] v oleic v linoleic v alpha-linolenic metabolites eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] omega-3 fatty acids). Changes were only observed for extreme diets, ie, those deficient in protein or very high in fat. Low-protein diet was the only condition in which the high metabolic efficiency characteristic of the refeeding period was partially suppressed, and this occurred despite a lack of concomitant reduction in body fat deposition. On the contrary, with high-fat diets (> 30% of dietary energy consumption) the elevated efficiency was further increased, an effect that was only partially accounted for by the lower energy cost of body fat gain from high-fat diets. These studies indicate that during body weight recovery, the mechanisms underlying the adaptive increase in metabolic efficiency favoring the replenishment of body fat stores override any effect of food type on thermogenesis, and suggest some convergence in the controlling neural pathway. The implications of these findings vis-a-vis nutritional rehabilitation (catch-up growth) and obesity relapse are discussed.
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PMID:Influence of dietary composition on energy expenditure during recovery of body weight in the rat: implications for catch-up growth and obesity relapse. 146 Nov 39

Efforts in Finland to implement the recommended non-pharmacological and pharmacological principles for the control of hypertension, stroke and ischaemic heart disease have been accompanied by an approximately 10 mm Hg fall in the population average of diastolic blood pressure, and about 60% decrease in deaths from both stroke and ischaemic heart disease among 30-59-year-old men and women from 1972 to 1992. Adherence to antihypertensive drug therapy has been quite good. However, the drug treatment does not seem to account for more than 5-6% of the observed fall of blood pressure, and 10-15% of the decrease in deaths from strokes and ischaemic heart disease. There has been no overall adherence to several non-pharmacological recommendations, and marked increases in the intake of alcohol, obesity among men, and smoking among women have been observed. However, the population adherence to recommendations to decrease the intakes of sodium and saturated fats, and to reduce the sodium-to-potassium ratio and the saturated-to-unsaturated fat ratio, has been good. These dietary changes appear to account for a major part of the fall of blood pressure and the decrease in the cardiovascular diseases. Currently a rapid further population-wide decrease in the dietary sodium-to-potassium ratio is taking place, due to a decrease in the use of salt and replacement of common salt by a novel sodium-reduced, potassium-, magnesium-, and l-lysine HCI-enriched salt, both in home kitchens and in the food industry.
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PMID:Adherence to and population impact of non-pharmacological and pharmacological antihypertensive therapy. 896 92

The obese Zucker rat represents a model of obesity combined with insulin resistance and hyperlipidaemia, which over a period of several months develops spontaneous glomerulosclerosis. The present study addressed the question as to whether glomerular sclerosis was associated with alterations in the degradation of matrix components. In the early phase (up to 6 months) glomeruli from obese rats displayed increased total collagen content (+64%) and decreased gelatinolytic activity (-34%) as compared to lean control animals. This decline in glomerular gelatinolytic activity was due to a reduction in gelatinase B [matrix metalloproteinase (MMP)-9]. Glomerular MMP-9 mRNA was reduced 4.6 +/- 0.6-fold (n = 3; p < 0.05), MMP-9 protein was not detectable by Western blotting and MMP-9 activity was considerably suppressed in gelatin zymograms. MMP-2, in terms of mRNA expression and activity, was unchanged. Tissue inhibitor of metalloproteinases (TIMP)-1 mRNA expression, TIMP-1 protein (immunohistochemistry) and TIMP-1 activity (reverse zymography) were enhanced in glomeruli from obese rats, while TIMP-2 mRNA remained unchanged. Moreover, mRNA for the alpha 1 IV collagen chain was 2.1 +/- 0.8-fold higher in glomeruli isolated from obese animals (n = 3; p < 0.05). These findings indicate that matrix expansion in glomeruli from obese Zucker rats is due to both enhanced synthesis of matrix components as well as reduced degradation by matrix metalloproteinases. Apparently the latter effect is based on a reduction in MMP-9 and up-regulation of its inhibitor TIMP-1.
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PMID:Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats. 930 Feb 40

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to the effects of lard, olive oil, safflower oil, or distilled water as the control on the development of insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous non-insulin-dependent diabetes mellitus (NIDDM) with obesity. After 17 or 18 weeks of treatment, the glucose infusion rate (GIR) in the euglycemic insulin-glucose clamp test only showed a significant increase in EPA-E-treated rats compared with control rats given distilled water alone as the vehicle. The GIR in EPA-E-treated animals was approximately three times greater than in the controls. This is the first report to display the influence of various fatty acids on the development of insulin resistance in OLETF rats. We demonstrated that EPA-E prevents the onset of insulin resistance, whereas olive oil and safflower oil have no effect and lard exacerbates insulin resistance. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase of the C18:2, C20:5, and C22:5 components in EPA-E-treated rats and, conversely, a significant decrease in C20:4. In addition, EPA-E-treated rats showed a significant increase in GLUT4 mRNA in skeletal muscle when compared with control rats. Our results indicate that the beneficial effect of EPA-E on insulin resistance in OLETF rats is likely to be dependent on modification of the phospholipid components of the skeletal muscle membrane. These findings suggest that dietary fatty acids may play a key role in the development of insulin resistance in patients with NIDDM.
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PMID:Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus. 943 43

The effects of n-3 polyunsaturated fatty acids (n-3PUFA) on obesity and diabetes were examined using KK-Ay mice fed with perilla oil (P), soybean oil (S), or lard (L), and those containing 30% fish oil (PF, SF, or LF), containing eicosapentaenoic acid (EPA = 9.9%) and docosahexaenoic acid (DHA = 18.0%). Perilla oil contained the largest proportion of linolenic acid (LNA = 61.9%). Computerized tomography (CT) scans showed narrower areas of visceral fat in the abdominal cross sections of groups given fish oil (PF, SF, and LF) and lower leptin levels (p < 0.05-p < 0.001) compared with controls (P, S, and L), without significant changes in energy intake and body weight. The highest plasma n-3PUFA content (21.31 +/- 0.35%) was attained with PF. This group contained 2.6-fold more plasma DHA (p < 0.001), and expressed 2.7-fold more UCP2 mRNA in white adipose tissue (p < 0.01) than in the P group. The epididymal fat pad (p < 0.05) weighed less, and levels of blood glucose (p < 0.05) and total cholesterol (p < 0.01) were reduced in PF compared with P.
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PMID:Increased uncoupling protein2 mRNA in white adipose tissue, and decrease in leptin, visceral fat, blood glucose, and cholesterol in KK-Ay mice fed with eicosapentaenoic and docosahexaenoic acids in addition to linolenic acid. 1033 20

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to lard on the development of hypertension and insulin resistance in Dahl salt-sensitive (Dahl-S) rats fed a high-sucrose diet (HSD), a model of salt-sensitive hypertension. After 16 weeks of treatment, the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test significantly increased in the HSD-EPA-E group compared with the HSD-water or -lard control group. The GIR was approximately three times higher in the HSD-EPA-E group versus the HSD-water or -lard control group, and it was about 70% of the rate in the calorically deprived control group fed a low-fat-high-fiber diet (LF-HFD). In addition, EPA-E significantly suppressed the elevation of plasma glucose and insulin levels after oral glucose loading. These results indicate that EPA-E prevents the development of insulin resistance in Dahl-S rats fed a HSD. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase in C18:2, C20:5, and C22:5 components in the HSD-EPA-E group and, conversely, a significant decrease in C16:0, C20:4, and C22:6. The present results indicate that the beneficial effect of EPA-E on insulin resistance in Dahl-S rats fed a HSD is likely dependent on the modification of phospholipid components in the skeletal muscle membrane. These findings suggest that EPA-E might prevent the development of insulin resistance in dietary obesity. In addition, the HSD-EPA-E group showed a significant increase in the level of uncoupling protein (UCP) in brown adipose tissue as compared with the HSD-water or -lard control group. However, EPA-E had no effect on the development of hypertension and obesity in Dahl-S rats fed the HSD.
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PMID:Effect of highly purified eicosapentaenoic acid ethyl ester on insulin resistance and hypertension in Dahl salt-sensitive rats. 1048 46

Hepatothermic therapy (HT) of obesity is rooted in the observation that the liver has substantial capacities for both fatty acid oxidation and for thermogenesis. When hepatic fatty acid oxidation is optimized, the newly available free energy may be able to drive hepatic thermogenesis, such that respiratory quotient declines while basal metabolic rate increases, a circumstance evidently favorable for fat loss. Effective implementation of HT may require activation of carnitine palmitoyl transferase-1 (rate-limiting for fatty acid beta-oxidation), an increase in mitochondrial oxaloacetate production (required for optimal Krebs cycle activity), and up-regulation of hepatic thermogenic pathways. The possible utility of various natural agents and drugs for achieving these objectives is discussed. Potential components of HT regimens include EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aspartate, chromium, coenzyme Q10, green tea polyphenols, conjugated linoleic acids, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs. Aerobic exercise training and very-low-fat, low-glycemic-index, high-protein or vegan food choices may help to establish the hormonal environment conducive to effective HT. High-dose biotin and/or metformin may help to prevent an excessive increase in hepatic glucose output. Since many of the agents contemplated as components of HT regimens are nutritional or food-derived compounds likely to be health protective, HT is envisioned as an on-going lifestyle rather than as a temporary 'quick fix'. Initial clinical efforts to evaluate the potential of HT are now in progress.
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PMID:Hepatothermic therapy of obesity: rationale and an inventory of resources. 1151 25

The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and 4 tissue inhibitors of MMPs (TIMPs) were measured by semiquantitative RT-PCR in adipose tissue isolated from mice maintained for 15 weeks on a standard or high-fat diet. In mice on standard diet, with the exception of MMP-8, all MMP and TIMP transcripts were detected in both gonadal and subcutaneous depots. In obese mice, the expression of MMP-3, -11, -12, -13, and -14 and TIMP-1 mRNAs was upregulated, whereas that of MMP-7, -9, -16, and -24 and TIMP-4 was downregulated. Most MMP and TIMP mRNAs were expressed at higher levels in stromal-vascular cells than in mature adipocytes. Analysis of adipose tissue by in situ fluorescent zymography revealed MMP-dependent proteolytic activities, demonstrating the presence of active MMPs in the intact tissue. In vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes was associated with substantial modulations of MMP and TIMP expression. Moreover, this in vitro adipogenesis was reduced in the presence of a synthetic MMP inhibitor. Thus, the adipose tissue expresses a large array of MMPs and TIMPs, which modulate adipocyte differentiation.
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PMID:Modulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity. 1191 31

Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling, a process that takes place during obesity-mediated adipose tissue formation. Here, we examine expression profiles and the potential role of MMPs and their tissue inhibitors (TIMPs) in adipose tissue remodeling during obesity. Expression patterns are studied by Northern blot and real-time PCR in two genetic models of obesity (ob/ob and db/db mice) and in a diet-induced model of obesity (AKR mice). Of the MMPs and TIMPs studied, mRNA levels for MMP-2, MMP-3, MMP-12, MMP-14, MMP-19, and TIMP-1 are strongly induced in obese adipose tissues compared with lean tissues. In contrast, MMP-7 and TIMP-3 mRNAs are markedly decreased in obesity. Interestingly, enzymatic activities of MMP-12 and of a new identified adipocyte-derived 30-kDa metalloproteinase are enhanced in obese adipose tissue fractions, demonstrating that MMP/TIMP balance is shifted toward increased matrix degradation in obesity. Finally, we analyze the modulation of MMP-2, MMP-19, and TIMP-1 during 3T3-L1 preadipocyte differentiation, and we explore the effect of inhibition of MMP activity on in vitro adipogenesis. We find that the synthetic MMP inhibitor BB-94 (Batimastat) decreases adipose conversion of 3T3-L1 and primary rat preadipocytes. BB-94 represses differentiation without affecting mitotic clonal expansion but prevents the early expression of CCAAT/enhancer-binding protein beta, a transcription factor that is thought to play a major role in the adipogenic program. Such findings support a role for the MMP/TIMP system in the control of proteolytic events and adipogenesis during obesity-mediated fat mass development.
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PMID:Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. 1252 76

Tissue inhibitor of matrix metalloproteinase-1 deficient (TIMP-1(-/-)) mice and wild-type (TIMP-1(+/+)) controls were kept on a standard (SFD) or a high fat diet (HFD) for 15 weeks. At the time of sacrifice, TIMP-1(-/-) mice on HFD had a significantly lower body weight (29 +/- 1.5 versus 41 +/- 1.8 g, p <0.005), and significantly less subcutaneous (0.81 +/- 0.19 versus 1.78 +/- 0.21 g, p <0.05) and gonadal (0.87 +/- 0.17 versus 1.85 +/- 0.18 g, p <0.005) fat mass. These differences were much less pronounced for mice on SFD. On HFD but not on SFD, adipocyte diameters were significantly lower in the adipose tissue of TIMP-1(-/-) mice. Plasma leptin levels in TIMP-1(-/-) mice on HFD were significantly lower as compared to TIMP-1(+/-) mice, and strongly correlated with adipose tissue mass for both genotypes. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density, larger stained area and vessel size in adipose tissue of TIMP-1(-/-) mice on HFD. This difference disappeared after normalization to the adipocyte number, suggesting that it does not represent a true enhancement of angiogenesis. Thus, in a murine model of nutritionally induced obesity, TIMP-1 promotes adipose tissue development.
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PMID:Deficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice. 1257 3


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