Capsaicin-sensitive afferent sensory nerves in modulating gastric mucosal defense against noxious agents.

In the rat stomach, evidence has been provided that capsaicin-sensitive sensory nerves (CSSN) are involved in a local defense mechanism against gastric ulcer. In the present study capsaicin or resiniferatoxin (RTX), a more potent capsaicin analogue, was used to elucidate the role of these sensory nerves in gastric mucosal protection, mucosal permeability, gastric acid secretion and gastrointestinal blood flow in the rat. In the rat stomach and jejunum, intravenous RTX or topical capsaicin or RTX effected a pronounced and long-lasting enhancement of the microcirculation at these sites, measured by laser Doppler flowmetry technique. Introduction of capsaicin into the rat stomach in very low concentrations of ng-microg x mL(-1) range protected the gastric mucosa against damage produced by topical acidified aspirin, indomethacin, ethanol or 0.6 N HCl. Resiniferatoxin exhibited acute gastroprotective effect similar to that of capsaicin and exerted marked protective action on the exogenous HCl, or the secretagogue-induced enhancement of the indomethacin injury. The ulcer preventive effect of both agents was not prevented by atropine or cimetidine treatment. Capsaicin given into the stomach in higher desensitizing concentrations of 6.5 mM markedly enhanced the susceptibility of the gastric mucosa and invariably aggravated gastric mucosal damage evoked by later noxious challenge. Such high desensitizing concentrations of capsaicin, however, did not reduce the cytoprotective effect of prostacyclin (PGI2) or beta-carotene. Capsaicin or RTX had an additive protective effect to that of atropine or cimetidine. In rats pretreated with cysteamine to deplete tissue somatostatin, capsaicin protected against the indomethacin-induced mucosal injury. Gastric acid secretion of the pylorus-ligated rats was inhibited with capsaicin or RTX given in low non-desensitizing concentrations, with the inhibition being most marked in the first hour following pylorus-ligation. Low intragastric concentrations of RTX reduced gastric hydrogen ion back-diffusion evoked by topical acidified salicylates. It is concluded that the gastropotective effect of capsaicin-type agents involves primarily an enhancement of the microcirculation effected through local release of mediator peptides from the sensory nerve terminals. A reduction in gastric acidity may contribute to some degree in the gastric protective action of capsaicin-type agents. The vasodilator and gastroprotective effects of capsaicin-type agents do not depend on vagal efferents or sympathetic neurons, involve prostanoids, histaminergic or cholinergic pathways.     

Androgens and body fat distribution

An important sex difference in body fat distribution is generally observed. Men are usually characterized by the android type of obesity, with accumulation of fat in the abdominal region, whereas women often display the gynoid type of obesity, with a greater proportion of their body fat in the gluteal-femoral region. Accordingly, the amount of fat located inside the abdominal cavity (intra-abdominal or visceral adipose tissue) is twice as high in men compared to women. This sex difference has been shown to explain a major portion of the differing metabolic profiles and cardiovascular disease risk in men and women. Association studies have shown that circulating androgens are negatively associated with intra-abdominal fat accumulation in men, which explains an important portion of the link between low androgens and features of the metabolic syndrome. In women, the low circulating sex hormone-binding globulin (SHBG) levels found in abdominal obesity may indirectly indicate that elevated free androgens are related to increased visceral fat accumulation. However, data on non SHBG-bound and total androgens are not unanimous and difficult to interpret for total androgens. These studies focusing on plasma levels of sex hormones indirectly suggest that androgens may alter adipose tissue mass in a depot-specific manner. This could occur through site-specific modulation of preadipocyte proliferation and/or differentiation as well as lipid synthesis and/or lipolysis in mature adipocytes. Recent results on the effects of androgens in cultured adipocytes and adipose tissue have been inconsistent, but may indicate decreased adipogenesis and increased lipolysis upon androgen treatment. Finally, adipose tissue has been shown to express several steroidogenic and steroid-inactivating enzymes. Their mere presence in fat indirectly supports the notion of a highly complex enzymatic system modulating steroid action on a local basis. Recent data obtained in both men and women suggest that enzymes from the aldoketoreductase 1C family are very active and may be important modulators of androgen action in adipose tissue.     

辣椒素敏感传入神经和NO中介大鼠胃扩张引起的胃酸分泌和胃粘膜血流量变化

目的和方法：本文采用氢气清除法测定胃粘膜血流量以及大剂量辣椒素使传入神经失去功能的技术,观察大鼠胃扩张过程中引起胃酸分泌和胃粘膜血流量(gastric mucosal blood flow,GMBF)的变化以及传入神经和内源性NO在这一效应中的作用。结果：①大鼠胃扩张引起胃酸分泌时GMBF增加。②预先用大剂量辣椒素消除传入神经作用可阻断胃扩张引起的GMBF脚增加效应,并部分阻断胃酸分泌。③预先静脉注射一氧化氮(nitric oxide,NO)生物合成阻断剂L-nitro-L-arginine methyl ester(L-NAME)胃扩张引起的GMBF增多效应消失,同时胃酸分泌减弱。结论：辣椒素敏感传入神经和内源性NO参与胃扩张引起的胃酸分泌及胃粘膜血流增多效应。     

Sodium-lithium countertransport and body fat distribution.

The relationship between erythrocyte sodium-lithium countertransport (Na-Li CT) and body fat distribution is analyzed in a sample (n = 101) of normotensive and untreated hypertensive men participating in an epidemiological study of coronary heart disease risk factors. Na-Li CT is significantly and positively associated with both subscapular skinfold and waist to hip ratio, but not with triceps skinfold. The univariate correlation between Na-Li CT and blood pressure is diminished when adjusted for body mass index and waist to hip ratio. These findings support the existence of an association between Na-Li CT and central body fat distribution and suggest that the metabolic abnormalities associated with centrally distributed body fat could explain, at least in part, the association between Na-Li CT and blood pressure. The maximal velocity of the sodium-lithium countertransport (Na-Li CT) in erythrocytes has been reported to be directly associated with blood pressure and hypertension in numerous reports from both clinical and epidemiological studies. In most of these studies, indices of weight and/or adiposity (body mass index, in particular) have been shown to be among the most important correlates of Na-Li CT. Adiposity is an important determinant of blood pressure, and there is evidence suggesting that the patterning of the fat cells in the body is linked to a number of metabolic disturbances that could lead to hypertension and an increase in other CHD risk factors. The present report analyses the relationship between Na-Li CT and body fat distribution in a sample of normotensive and untreated hypertensive men participating in an epidemiological study.     

Effect of body fat and gender on body temperature distribution

It is well known that body composition can influence peripheral heat loss and skin temperature. That the distribution of body fat is affected by gender is well known; however, there is little information on how body composition and gender influences the measure of skin temperature. This study evaluated skin temperature distribution according to body fat percentage (BF%) and gender. A sample of 94 apparently healthy volunteers (47 women and 47 men) was assessed with Dual-Energy X-Ray Absorptiometry (DXA) and infrared thermography (mean, maximum and minimum temperatures – T_Mean, T_Max and T_Min). The sample was divided into groups, according to health risk classification, based on BF%, as proposed by the American College of Sports Medicine: Average (n = 58), Elevated (n = 16) or High (n = 20). Women had lower T_Mean in most regions of interest (ROI). In both genders, group High had lower temperature values than Average and Elevated in the trunk, upper and lower limbs. In men, palms and posterior hands had a tendency (p < 0.05) for increased temperature along with increased BF%. T_Mean, T_Max and T_Min of trunk, upper and lower limbs were negatively correlated with BF% and the fat percentage of each segment (upper limbs, lower limbs and trunk). The highest correlations found in women were between posterior trunk and BF% (rho = −0.564, p < 0.001) and, in men, between anterior trunk and BF% (rho = −0.760, p < 0.001). Overall, this study found that women have lower skin temperature than men, which was related with higher BF%. Facial temperature seems not to be influenced by body fat. With the future collection of data on the relationship between BF% and skin temperature while taking into account factors such as body morphology, gender, and ethnicity, we conclude that measurement of BF may be reliably estimated with the use of thermal imaging technology.     

Activation of rat intestinal mucosal mast cells by fat absorption

Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D(2) (PGD(2)) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD(2), ～20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent.     

Monogenic disorders of obesity and body fat distribution.

Recently, great progress has been made towards understanding the molecular basis of body fat regulation. Identification of mutations in several genes in spontaneous monogenic animal models of obesity and development of transgenic models have indicated the physiological roles of many genes in the regulation of body fat distribution. In humans, mutations in leptin, leptin receptor, prohormone convertase 1 (PC1), pro-opiomelanocortin (POMC), melanocortin 4-receptor (MC4-R), and peroxisome proliferator-activated receptor (PPAR) gamma2 genes have been described in patients with severe obesity. Most of these obesity disorders exhibit a distinct phenotype with varying degrees of hypothalamic and pituitary dysfunction and a recessive inheritance, whereas MC4-R mutation has a nonsyndromic phenotype with dominant inheritance. These mutations suggest the critical role of central signaling systems composed of leptin/leptin receptor and alpha-melanocyte stimulating hormone/MC4-R in human energy homeostasis. Although the genetic basis of monogenic disorders of body fat distribution, such as congenital generalized lipodystrophy and familial partial lipodystrophy, Dunnigan variety, is still unknown, the genes for these have recently been localized to chromosomes 9q34 and 1q21-22, respectively. The advances in our knowledge of the phenotypic manifestations and underlying molecular mechanisms of genetic body fat disorders may lead to better treatment and prevention of obesity and other disorders of adipose tissue in the future.     

The relationship between aromatase activity and body fat distribution

The metabolism of androstenedione (A) to estrone (E1) and 5 alpha-reduced androgens was studied in stromal cells derived from human adipose tissue from different body sites. The tissue was obtained from non-obese patients undergoing cosmetic liposuction or at the time of surgery for reduction mammoplasty. The conversion of A to E1 per 1x 10(6) cells was between 6- and 30-fold greater in the upper thigh, buttock, and flank than in the abdomen. These differences were present in primary culture and persisted to at least the third subculture. Estrogen formation in breast adipose tissue was similar to that found in cells from abdominal fat. The formation of 5 alpha-reduced metabolites (5 alpha-androstenedione, androsterone, and dihydrotestosterone) varied from patient to patient but was similar in cells from different body sites. These studies show that the regional distribution of fat may influence the metabolism of androgens in adipose tissue, with upper body fat tending to form a lower ratio of estrogens to 5 alpha-reduced androgens than lower body fat.     

The effect of body fat percentage and body fat distribution on skin surface temperature with infrared thermography

This study aimed to search for relations between body fat percentage and skin temperature and to describe possible effects on skin temperature as a result of fat percentage in each anatomical site. Women (26.11±4.41 years old) (n =123) were tested for: body circumferences; skin temperatures (thermal camera); fat percentage and lean mass from trunk, upper and lower limbs; and body fat percentage (Dual-Energy X-Ray Absorptiometry). Values of minimum (T_Mi), maximum (T_Ma), and mean temperatures (T_Me) were acquired in 30 regions of interest. Pearson's correlation was estimated for body circumferences and skin temperature variables with body fat percentage. Participants were divided into groups of high and low fat percentage of each body segment, of which T_Me values were compared with Student's t-test. Linear regression models for predicting body fat percentage were tested. Body fat percentage was positively correlated with body circumferences and palm temperatures, while it was negatively correlated with most temperatures, such as T_Ma and T_Me of posterior thighs (r =−0.495 and −0.432), T_Me of posterior lower limbs (r =−0.488), T_Ma of anterior thighs (r =−0.406) and T_Mi and T_Me of posterior arms (r =−0.447 and −0.430). Higher fat percentages in the specific anatomical sites tended to decrease T_Me, especially in posterior thighs, shanks and arms. Skin temperatures and body circumferences predicted body fat percentage with 58.3% accuracy (R =0.764 and R² =0.583). This study clarifies that skin temperature distribution is influenced by the fat percentage of each body segment.     

Relation between leptin and body fat distribution in menopausal status

We examined the serum concentrations of leptin in a homogeneous group of 52 postmenopausal Mediterranean women, calculating body fat mass distribution by waist-to-hip circumference ratio (WHR) and other anthropometric measurements. Significant correlations were found between leptin and weight (r=0.59), Body Mass Index (BMI) (r=0.56), Conicity Index (CI) (r=0.49) and all circumferences measured: chest (r=0.55), waist (0.61) and hip (r=0.65), but not between leptin and WHR. Leptin levels does not seem to be influenced by fat mass distribution (android or gynoid type) while weight gain over life appears to be related with the hormone concentration when menopausal status is well established.     

Postmenopausal sex hormones in relation to body fat distribution

Being overweight or obese increases the risk of postmenopausal breast cancer. A potential reason may be the frequently observed positive association of BMI with endogenous sex hormones and its negative association with sex hormone-binding globulin (SHBG). The purpose of this study was to investigate whether a woman's body fat distribution shows a BMI-independent association with these breast cancer-related biomarkers. Performing cross-sectional analyses among 1,180 postmenopausal women, we assessed whether associations of surrogates for an abdominal (waist circumference; waist-to-hip ratio, WHR) and gluteofemoral (hip circumference) fat distribution with estrone, total and free estradiol, androstenedione, total and free testosterone, and SHBG changed after adjustment for, or stratification by, BMI. All anthropometric measures were positively associated with estrogens and free testosterone, and negatively with SHBG. After adjustment for BMI, associations of free estradiol, free testosterone, and SHBG with both waist circumference and WHR remained significant, but all initially significant associations with hip circumference were abolished. In stratified analyses, waist circumference and WHR correlated with free estradiol, free testosterone, and SHBG in women with a BMI < 30 kg/m(2) but not in women with a BMI ≥ 30 kg/m(2). The latter suggests that in obese women, a possibly unique effect of abdominal fat on these biomarkers may be masked by the already large amount of overall body fat. On the whole, our results indicate that waist circumference and WHR, but not hip circumference, are associated with SHBG and SHBG-related sex hormones (free estradiol and free testosterone) independently of BMI.     

Anthropometric measures, body composition, body fat distribution, and knee osteoarthritis in women

Objective: Increased BMI is a well‐recognized risk factor for radiographic knee osteoarthritis (rKOA); however, the contributions of the components of body composition, body fat distribution, and height to this association are not clear. Research Methods and Procedures: We examined 779 women ≥45 years of age from the Johnston County Osteoarthritis Project. Body composition was assessed using DXA, and rKOA was defined as Kellgren‐Lawrence grade ≥2. Logistic regression models examined the association between rKOA and the fourth compared with the first quartiles of anthropometric, body composition, and fat distribution measures adjusting for age, ethnicity, and prior knee injury. Results: The adjusted odds ratios and 95% confidence interval of BMI and weight were 5.27 (3.05, 9.13) and 5.28 (3.05, 9.16), respectively. In separate models, higher odds of rKOA were also found for fat mass [4.54 (2.68, 7.69)], percent fat mass [3.84 (2.26, 6.54)], lean mass [3.94 (2.22, 6.97)], and waist circumference [4.15 (2.45, 7.02)]. Waist‐to‐hip ratio was not associated with rKOA [1.45 (0.86, 2.43)], and percent lean mass was associated with lower odds [0.20 (0.11, 0.35)]. Taller women had higher odds of rKOA after adjustment for BMI [1.77 (1.05, 3.00)]. Discussion: This study confirms that BMI and weight are strongly associated with rKOA in women and suggests that precise measurements of body composition and measures of fat distribution may offer no advantage over the more simple measures of BMI or weight in assessment of risk of rKOA.     

Body fat, abdominal fat, and body fat distribution is related to left atrial diameter in young children

In adults, the size of the left atria (LA) has important prognostic information. In obese adults, adolescents and children enlargement of LA have been observed. This has not been investigated on a population-based level in young children. We therefore assessed if total body fat mass (TBF), abdominal fat, and body fat distribution were related to LA diameter. Cross-sectional study of 244 children (boys = 137 and girls n = 107) aged 8-11 years, recruited from an urban population-based cohort. Dual-energy X-ray absorptiometry (DXA) measured total lean body mass, TBF, and abdominal fat mass (AFM). Body fat was also calculated as a percentage of body mass (BF%). Body fat distribution (AFM/TBF) was calculated. Echocardiography was performed with two-dimensional guided M-mode. LA diameter was measured and left ventricular mass (LVM) was calculated. Systolic blood pressure and diastolic blood pressure were measured and maturity assessed according to Tanner. There were significant (P < 0.05) univariate correlations for all children between TBF (r = 0.40), BF% (r = 0.32), AFM (r = 0.41), and AFM/TBF (r = 0.41) vs. LA diameter. Multiple regression analyses with the inclusion of possible confounders such as lean body mass, blood pressure, gender, age, and Tanner stage revealed that TBF, AFM, and AFM/TBF were all independently related to LA diameter. Differences in the different body fat measurements explained 6-9% of the variance in LA size. These results demonstrated that both total body fat, AFM, and body fat distribution are already at a young age negatively and independently associated to LA diameter.     

肠道黏膜免疫与炎症小体的研究进展

肠道是机体消化器官,为机体生命活动提供所需要的营养。肠道免疫系统有独特的功能,在抵抗潜在病原体侵入机体过程中发挥至关重要的作用。炎症小体是机体天然免疫系统中重要的蛋白复合体感受器,参与病原体引起的宿主防御反应,并在维持肠道免疫稳态中发挥关键作用。本文综述了肠道黏膜免疫系统及炎症小体在肠道免疫中的作用。