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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a multifactorial disease that arises from complex interactions between genetic predisposition and environmental factors. It increases a risk of cardiovascular and metabolic diseases such as diabetes, hypertension, and hyperlipidemia. Recent molecular genetic studies have disclosed some monogenic forms of obesity in humans. Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus. alpha-melanocyte stimulating hormone (alpha-MSH) derived from proopiomelanocortin (POMC) and melanocortin-4 receptor (MC4-R) have been reported to be involved in the downstream of leptin actions. In this paper, we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin-4 receptor.
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PMID:[Obesity induced by abnormality in leptin receptor and melanocortin-4 receptor]. 1185 34

Obesity, which has reached epidemic proportions in the United States and other western countries, may be complicated by hypertension, an increased incidence of renal cancer or proteinuria. Patients with obesity-associated proteinuria show focal glomerulosclerosis and glomerulomegaly on biopsy, usually have minimal clinical edema and relatively normal levels of serum albumin, cholesterol and blood pressure, and can progress to end-stage renal disease. Severe obesity may also be an additive risk factor in patients with preexisting nephropathy or reduced renal mass. The pathophysiology of obesity-associated proteinuria is unclear but may include hyperfiltration, increased renal venous pressure, glomerular hypertrophy, hyperlipidemia and increased synthesis of vasoactive and fibrogenic substances, including angiotensin II, insulin, leptin and transforming growth factor-beta1. These substances may individually or interactively affect glomerular hyperfiltration, mesangial cell hypertrophy and matrix production, and the production of collagen, fibronectin, transforming growth factor-beta and other fibrogenic mediators of change. Although angiotensin-converting enzyme inhibition has proven to have an impact, perhaps temporarily, on obesity-associated proteinuria in humans, weight reduction early in the course of the disease would appear the most important therapeutic approach.
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PMID:Obesity and renal disease. 1198 Dec 64

Thyroid hormones (TH) are potent modulators of adaptive thermogenesis and can potentially contribute to development of obesity. The decrease of T(3) in association with reduction of calorie intake is centrally regulated via decreases in leptin and melanocortin concentrations and peripherally via a decrease in deiodinase activity, all aimed at protein and energy sparing. The use of TH in the treatment of obesity is hardly justified except in cases of elevated thyrotropin (TSH) with low/normal T(3) and T(4) and/or a low T(3) or T'(3)/T(4) or a high TSH/T(3) ratio. TH treatment with small doses of T(3) can also be exceptionally applied in obese patients resistant to dietary therapy who are taking beta-adrenergic blockers or with obesity developed after cessation of cigarette smoking and with hyperlipidemia and a concomitant high thryrotropin/T(3) ratio. Supplementation with Se(2+) and Zn(2+) may be tried along with more severe calorie restriction to prevent decline of T(3).
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PMID:Thyroid hormones in the pathogenesis and treatment of obesity. 1200 27

Low-glycemic index diets are associated with a wide range of benefits when followed on a chronic basis. The chronic effects, however, of the substitution of 1 meal per day are not well known in diabetic subjects. Therefore, we aimed to evaluate whether the chronic use of a low-glycemic index breakfast (low-GIB) rich in low-GI carbohydrates and a modest amount of soluble fibers could have an effect on lipemia at a subsequent lunch, and improve glucose and lipid metabolism in men with type 2 diabetes. A total of 13 men with type 2 diabetes were randomly allocated in a double-blind cross-over design to a 4-week daily intake of a low-GI versus a high-GI breakfast separated by a 15-day washout interval. The low-GI breakfast was composed of whole grain bread and muesli containing 3 g beta-glucan from oats. Low-GIB induced lower postprandial plasma glucose peaks than the high-GIB at the beginning (baseline, P <.001) and after the 4-week intake (P <.001). The incremental area under the plasma glucose curve was also lower (P <.001, P <.01, baseline, and 4 weeks, respectively). There was no effect on fasting plasma glucose, insulin, fructosamine, or glycosylated hemoglobin (HbA(1c)). Fasting plasma cholesterol, as well as the incremental area under the cholesterol curve, were lower (P <.03, P <.02) after the 4-week low-GIB period than after the high-GIB period. Apolipoprotein B (apo B) was also decreased by the 4-week low-GIB. There was no effect of the low-GI breakfast on triacylglycerol excursions or glucose and insulin responses at the second meal. The high-GIB, however, tended to decrease the amount of mRNA of leptin in abdominal adipose tissue, but had no effect on peroxisome proliferator-activated receptor gamma (PPARgamma) and cholesterylester transfer protein (CETP) mRNA amounts. In conclusion, the intake of a low-GI breakfast containing a modest amount (3 g) of beta-glucan for 4 weeks allowed good glycemic control and induced low plasma cholesterol levels in men with type 2 diabetes. The decrease in plasma cholesterol associated with low-GI breakfast intake may reduce the risk of developing cardiovascular complications in subjects with type 2 diabetes.
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PMID:Four-week low-glycemic index breakfast with a modest amount of soluble fibers in type 2 diabetic men. 1207 24

The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic animal model that exhibits obesity, metabolic features of hyperinsulinemia, hyperglycemia, and hyperlipidemia, which are characteristic of type II diabetes and mild hypertension. To determine the role of leptin, the protein product of the ob gene, in the development of obesity and diabetes in this model, we measured steady-state circulating levels of leptin in obese and lean SHR/N-cp rats and examined the relation between plasma leptin levels and metabolic variables at the stage of established obesity in these animals. Mean fasting plasma leptin concentration was 8-fold higher in obese than in lean rats (p < 0.01). This was associated with a 6-fold elevation in plasma insulin in the obese group. Fasting levels of plasma glucose, cholesterol, and triglyceride were all significantly higher in obese rats than in lean controls. Spearman correlation analysis showed a significant positive correlation between plasma leptin concentration and body weight among the animals (r = 0.73, p < 0.01). Similarly, plasma insulin concentration was significantly correlated with BW in all animals (r = 0.54, p < 0.05). There was also a significant positive correlation between plasma leptin and plasma insulin in the entire group (r = 0.70, p < 0.01). However, this relationship was significant only for lean rats but not for obese rats (r = 10.59, p < 0.05 for lean rats, and r = 0.23, p = NS, for obese rats). Plasma leptin also correlated positively with fasting plasma glucose (r = 0.75, p < 0.05), total cholesterol (r = 0.63, p < 0.05), and triglyceride (r = 0.67, p < 0.05). The marked elevation of plasma leptin in obese SHR/N-cp rats suggests that obesity in this animal model is related to up-regulation of the ob gene. Circulating leptin appears to be one of the best biological markers of obesity and that hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in the diabesity syndrome.
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PMID:Leptin and its relation to obesity and insulin in the SHR/N-corpulent rat, a model of type II diabetes mellitus. 1236 10

The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents. In contrast, information regarding the roles of this hormone in humans is limited. Three morbidly obese children, who were congenitally deficient in leptin, were treated with daily subcutaneous injections of recombinant human leptin for up to 4 years with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia. Leptin therapy resulted in a rapid and sustained increase in plasma thyroid hormone levels and, through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development. Leptin deficiency was associated with reduced numbers of circulating CD4(+) T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration. The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency.
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PMID:Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. 1239 45

Highly active antiretroviral therapy, which includes a combination of protease inhibitors, is highly successful in controlling human immunodeficiency virus (HIV) infection and reducing the morbidity and mortality of autoimmune deficiency syndrome (AIDS). However, the benefits of HIV protease inhibitors are compromised by numerous undesirable side effects. These include peripheral fat wasting and excessive central fat deposition (lipodystrophy), overt hyperlipidemia, and insulin resistance. The mechanism associated with protease inhibitor-induced metabolic abnormalities is multifactorial. One major effect of the protease inhibitor is its suppression of the breakdown of the nuclear form of sterol regulatory element binding proteins (nSREBP) in the liver and adipose tissues. Hepatic accumulation of nSREBP results in increased fatty acid and cholesterol biosynthesis, whereas nSREBP accumulation in adipose tissue causes lipodystrophy, reduces leptin expression, and promotes insulin resistance. The HIV protease inhibitors also suppress proteasome-mediated breakdown of nascent apolipoprotein (apo) B, thus resulting in the overproduction and secretion of triglyceride-rich lipoproteins. Finally, protease inhibitor also suppresses the inhibition of the glucose transporter GLUT-4 activity in adipose and muscle. This latter effect also contributes directly to insulin resistance and diabetes. These adverse effects need to be alleviated for long-term use of protease inhibitor therapy in treatment of HIV infection.
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PMID:Effects of HIV protease inhibitor therapy on lipid metabolism. 1254 52

It is generally accepted that obesity is associated with many other multiple-risk factor syndromes such as hypertension, hyperlipidemia, type 2 diabetes mellitus, and periodontal disease. The number of obese people is increasing rapidly in both western and eastern countries. Adipocytes in the adipose tissues of obese people produce large quantities of biologically active molecules such as leptin, an important molecule regulating energy expenditure and body weight. Therefore, adipocyte-derived active molecules, named adipocytokines, are candidate molecules accounting for the close association between obesity and other multiple-risk factor syndromes. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is produced by adipocytes, and its blood concentration is elevated in obese patients and declines with weight loss. Studies have demonstrated that TNF-alpha suppresses insulin action via its specific receptor; hence, it exacerbates insulin resistance. In addition to adipocytes, monocytes/macrophages produce large quantities of TNF-alpha. Thus, TNF-alpha, produced from monocytic cells due to inflammatory diseases, may have an additive influence on insulin sensitivity to adipocyte-derived TNF-alpha. Here, we hypothesized that 1) TNF-alpha produced by the adipose tissues of obese patients acts as a risk factor for periodontal inflammation, and 2) TNF-alpha produced due to periodontal inflammation may be an additional important factor influencing insulin sensitivity in both obese and type 2 diabetic patients. We believe that this interaction is a possible mechanism accounting for a 2-way relationship between type 2 diabetes and periodontal disease.
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PMID:Periodontal disease and diabetes mellitus: the role of tumor necrosis factor-alpha in a 2-way relationship. 1259 3

We measured serum leptin levels in two groupings of wild male baboons, one with access to abundant quantities of food from gardens and garbage dumps near human habitations (Garbage; n = 11) and one without access (No Garbage; n = 10). A Garbage subgroup had high leptin levels (Garbage HL), whereas the rest of the Garbage group had low leptin levels (Garbage LL) similar to those in the No Garbage group. The Garbage HL individuals were obese, with higher mass, body mass index, and leptin to mass ratios; were insulin to resistant, with elevations in serum insulin, glucose, and insulin to glucose ratios; and were hyperlipidemic. This syndrome X-like condition occurred only in the Garbage HL subset. The Garbage LL subset did not differ from the No Garbage individuals in mass, body mass index, leptin to mass ratio, insulin, glucose, or insulin to glucose ratios. The highest cholesterol levels, however, occurred in the Garbage LL individuals, suggesting that susceptibility to hyperlipidemia is distinguishable from susceptibility to obesity and insulin resistance. The differences were not explained by age or social status. These results show that a subgroup of wild baboons is susceptible to developing obesity and insulin resistance and that this susceptibility is not related to age or social rank.
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PMID:Serum leptin levels as a marker for a syndrome X-like condition in wild baboons. 1262 12

Recent findings indicate that in addition to its hyperlipemic effect, a high fructose diet has a pro-oxidant effect in rats compared with a starch-based diet. Oligofructose (OFS) has already been shown to decrease plasma lipids in rats. We assessed the impact of fructose on oxidative stress by supplementing a high fructose diet with OFS. Rats were fed either a high fructose diet or a starch-based diet, with or without supplementation of 10 g/100 g oligofructose for 4 wk. Regardless of the type of carbohydrate, OFS in the diet produced an enlargement of the cecum and led to a significant increase in the SCFA cecum pool. Fructose feeding was associated with significantly higher insulin plasma concentrations (+63%) in the control groups, whereas insulin plasma concentrations did not differ in rats fed the fructose diet supplemented with OFS. Plasma leptin concentration was significantly lower (approximately 50%) in the OFS-supplemented fructose group compared with the other three groups. Fructose feeding in rats also significantly increased plasma (P < 0.001) and liver (P < 0.001) triglyceride (TG) concentrations and the addition of OFS prevented the TG accumulation induced by fructose in the liver (P < 0.05) and hyperlipemia (P < 0.05). OFS consumption prevented (P < 0.05) the lower plasma vitamin E/TG ratio in rats fed the fructose diet. Control rats fed the fructose diet had high plasma TBARS values compared with rats fed the starch diet, whereas TBARS values remained unchanged when rats were supplemented with OFS. Control rats fed the fructose diet had higher TBARS urine values and higher heart tissue susceptibility to peroxidation compared with rats fed the starch diet, and this effect was significantly reduced by OFS consumption. Further studies are required to identify the mechanisms underlying the protective effect of OFS against the pro-oxidant effect of fructose. However, the potential nutritional benefits of OFS supplementation in fructose-rich diets are suggested.
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PMID:Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. 1277 37


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