Different Associations of Trunk and Lower-Body Fat Mass Distribution with Cardiometabolic Risk Factors between Healthy Middle-Aged Men and Women.

The aim of this study was to assess whether the gender-specific pattern of fat mass (FM) distribution is related to gender differences in cardiometabolic risk factors. 207 healthy middle-aged Japanese were included in the study. We measured FM in the total body, trunk, and lower-body with dual-energy X-ray absorptiometry (DXA). The percentage of trunk FM (TFM) and lower-body FM (LFM) is noted as %TFM and %LFM, respectively. Other measurements included glucose and insulin during oral glucose tolerance test (OGTT), leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and systemic oxidative stress marker. Arterial properties were indicated by cardio-ankle vascular index (CAVI) and intima-media thickness (IMT) of the common carotid artery. The results showed that %TFM is higher whereas %LFM is lower in men than in women and men have a more atherogenic cardiometabolic profile. In both genders, %TFM (%LFM) is related to an unfavorable (favorable) cardiometabolic profile. In particular, the relation between %LFM and OGTT-derived insulin sensitivity index is stronger in women than in men. These findings suggested that in relatively healthy adults, android and gynoid pattern of FM distribution contributes to gender differences in cardiometabolic risk factors.

Associations of lower-body fat mass with favorable profile of lipoproteins and adipokines in healthy, slim women in early adulthood.

AIM: We determined the association of lower-body fat mass (LFM) and trunk fat mass (TFM) with cardiometabolic risk factors and adipokines in young, healthy, slim women. METHODS: A total of 481 college female students underwent the following: regional body fat distribution as assessed by dual energy X-ray absorptiometry (DXA), a 75g oral glucose tolerance test (OGTT) and fasting blood sampling for measurement of lipids, lipoproteins, apolipoproteins (apo), liver enzymes and adipokines. RESULTS: After adjusting for TFM, LFM was positively associated with HDL cholesterol, adiponectin, pre-heparin lipoprotein lipase and insulin sensitivity, as estimated by the Matsuda index, whereas it was negatively related to triglycerides, apo B, apo B/A1 ratio, small dense LDL, FFA, glucose and insulin at 2h during OGTT, area under the curve of insulin response during OGTT and the white blood cell count. Participants were divided into 9 groups according to tertiles of TFM and LFM. In the middle tertile of TFM, HDL cholesterol and adiponectin increased and triglycerides, apoB/A1 ratio and plasminogen-activator inhibitor-1 decreased from the low to high LFM tertiles. Gamma-glutamyltransferase levels in middle and high LFM tertiles were lower than in the lower LFM tertile. CONCLUSION: For a given level of trunk fat mass, a higher lower-body fat mass is associated with an advantageous profile of not only blood lipoproteins but also serum adipokines, even in healthy, slim women in early adulthood.

Associations of 18-year-old daughters' and mothers' serum leptin, body mass index and DXA-derived fat mass.

AIM AND METHODS: We assessed the relationship of the body mass index (BMI) of 187 college female students aged 18 years with the reported BMI of their middle-aged biological parents measured on 2 occasions: when the parents were 18-20 years old and at the time of the study. The relationships of fat mass measured using whole body dual energy X-ray absorptiometry (DXA) and serum leptin levels were also determined between 148 daughters and middle-aged parents (148 mothers and 59 fathers). RESULTS: The BMI of daughters was associated with their mothers' BMI (r=0.30, p<0.0001) but not with their fathers' BMI measured when they were 18 years old. Daughters' BMI showed a stronger association with the current BMI of their mothers BMI (r=0.36, p<0.0001) than that of their fathers' BMI (r=0.19, p=0.01). In addition, the serum leptin levels of daughters were correlated with their mothers' leptin values (r=0.22, p=0.04). Further, not only total body fat mass (r=0.19, p<0.05) but also fat mass in the trunk (r=0.18, p<0.05) and legs (r=0.17, p<0.05) was associated between daughters and their mothers. CONCLUSION: The significant correlation between daughters' and mothers' BMI measured when their mothers were 18 years old did not result from shared environmental factors, including the intrauterine environment. The results in the present study therefore suggest that adiposity in 18-year-old daughters may be influenced by the maternal effect. The associations of serum leptin and DXA-derived fat mass between daughters and their mothers may support our hypothesis.

Relationships of systemic oxidative stress to body fat distribution, adipokines and inflammatory markers in healthy middle-aged women.

Obesity and systemic oxidative stress are closely related. However data concerning the relationships between oxidative stress and body fat mass distribution are sparse. Anthropometric and metabolic profile was evaluated in 148 clinically healthy middle-aged women to assess the correlations between oxidative stress, fat mass distribution, adipokines, and inflammatory markers. Systemic oxidative stress was assessed by urinary creatinine-indexed 8-epi-prostaglandin F-(2alpha) (8-epi-PGF(2alpha)). Body fat mass distribution was examined by dual-energy X-ray absorptiometry (DXA). Lipid profile, adipokines and inflammatory markers including leptin, adiponectin, high sensitive C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-alpha (TNF-alpha) were determined. We found body mass index (BMI), waist circumference (WC), both central and peripheral DXA-derived regional fat mass (FM) accumulations were positively correlated with 8-epi-PGF(2alpha). Leptin, hsCRP and PAI-1also positively associated with 8-epi-PGF(2alpha). After adjustment for BMI and WC, lower-body FM, total FM and PAI-1 retained significant association with 8-epi-PGF(2alpha). Mutliple linear regression analyses indicated lower-body FM and PAI-1 were the two important predicators of 8-epi-PGF(2alpha). These results suggest that DXA-derived regional FM indices, especially low extremity adiposity, are more closely associated with systemic oxidative stress than indirect anthropometric indices. Positive associations between 8-epi-PGF(2alpha) and PAI-1, hsCRP, leptin support the notion that oxidative-stress-induced dysregulation of inflammation and adipokines may mediate the obesity-related metabolic derangement.

PKClambda regulates glucose-induced insulin secretion through modulation of gene expression in pancreatic beta cells.

Altered regulation of insulin secretion by glucose is characteristic of individuals with type 2 diabetes mellitus, although the mechanisms that underlie this change remain unclear. We have now generated mice that lack the lambda isoform of PKC in pancreatic beta cells (betaPKClambda(-/-) mice) and show that these animals manifest impaired glucose tolerance and hypoinsulinemia. Furthermore, insulin secretion in response to high concentrations of glucose was impaired, whereas the basal rate of insulin release was increased, in islets isolated from betaPKClambda(-/-) mice. Neither the beta cell mass nor the islet insulin content of betaPKClambda(-/-) mice differed from that of control mice, however. The abundance of mRNAs for Glut2 and HNF3beta was reduced in islets of betaPKClambda(-/-) mice, and the expression of genes regulated by HNF3beta was also affected (that of Sur1 and Kir6.2 genes was reduced, whereas that of hexokinase 1 and hexokinase 2 genes was increased). Normalization of HNF3beta expression by infection of islets from betaPKClambda(-/-) mice with an adenoviral vector significantly reversed the defect in glucose-stimulated insulin secretion. These results indicate that PKClambda plays a prominent role in regulation of glucose-induced insulin secretion by modulating the expression of genes important for beta cell function.

Normalization of blood glucose after islet cografting with placental tissues in diabetic mice.

A fetus in the uterus is not rejected at any time during the entire gestational period, even without the administration of immunosuppressive agents, though fetus is a kind of allograft. This prevention of rejection is considered to be associated with the presence of placental tissues. This hypothesis was tested by the allografting of islets together with placental tissues (trophoblasts) in streptozotocin (STZ)-induced diabetic mice. Placentae were harvested from the mice at the 14th postgestation day by being peeled off carefully and with the maternal decidua left behind, and cut into small pieces. Five hundred freshly isolated islets together with placental tissues obtained from ICR mice were placed under the left kidney capsule of STZ-induced diabetic C57BL/6J mice. The nonfasting blood glucose level was reduced from 477 +/- 41 mg/dl at the time of pretransplant to that of the intact normal mice (161 +/- 18 mg/dl) soon after the cografting, and did not return to the pretransplant level before the 14th posttransplant day. The grafting of the same number of islets alone and/or liver tissues dropped the blood glucose level, but not to that of the intact normal mice. It returned to the pretransplant level within 1 week. This is the first successful prolongation of survival of allografted islets without immunosuppressive agents through cotransplantation of allogenic placental tissues. The underlying mechanism remains to be clarified.