K.-L. Catherine Jen

High fat feeding is associated with increased blood pressure, sympathetic nerve activity and hypothalamic mu opioid receptors

Obesity and high fat diets are associated with an increased prevalence of diabetes, cardiovascular disease, and hypertension. However, the mechanism(s) linking obesity and high fat diet to these metabolic and cardiovascular disorders are not fully elucidated. Leptin stimulates the formation of pro-opiomelanocortin and its products. The stimulation of the central nervous system (CNS) opioids and their receptors is associated with an increase in cardiovascular dynamics. In this study we hypothesized that obesity changed the CNS opioids and their receptors that could play a role in altered cardiovascular and autonomic nervous regulation in obesity. Male Wistar rats were fed either a high fat (HF) or regular chow (control) diet. After 12 weeks, rats were anesthetized and instrumented to record mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). A blood sample was collected and plasma glucose, insulin, leptin, beta-endorphins were measured. The brains were subsequently processed for immunohistochemistry and in situ hybridization. The HF rats were larger and had a greater percentage of body fat. Leptin and insulin levels were also higher in the HF animals. Basal MAP and RSNA were significantly higher in HF rats. Additionally, immunohistochemistry and in situ hybridization demonstrated that HF rats had increased hypothalamus mu opioid receptors compared to controls. These studies suggest that HF feeding is associated with increased body fat, plasma leptin, insulin, and hypothalamic mu opioid receptors. The increased mu opioid receptors may contribute to the higher MAP and RSNA observed in HF animals.

Obesity due to high fat diet decreases the sympathetic nervous and cardiovascular responses to intracerebroventricular leptin in rats

Obesity is associated with an increase in plasma leptin levels primarily derived from enhanced expression of the leptin gene in the adipose tissue. Leptin levels and expression are higher in females than males. The main functions of leptin are to decrease food intake and increase sympathetic nerve activity, especially in the brown adipose tissue. The high levels of leptin in obese, female rats suggest leptin resistance. In this article we describe experiments designed to investigate the effect of the intracerebroventricular (i.c.v.) administration of leptin on lumbar sympathetic nerve activity (LSNA) and cardiovascular parameters in female rats fed a low fat diet (control), a high fat diet (obese), or high fat diet followed by a period of food restrictions (reduced). The i.c.v. leptin administration increased LSNA in control rats, but decreased it in obese rats. In weight reduced animals the LSNA response to leptin returned to control levels. The i.c.v. leptin increased the mean arterial pressure in control and wt. reduced rats, but not in obese animals. The heart rate did not respond to leptin in any animal group. These results suggest that obesity decreases the central nervous system (CNS)-mediated lumbar sympathetic nervous and cardiovascular responses to leptin and that these responses recover following food restriction and wt. reduction. We conclude that obesity is associated with a decreased CNS response to leptin leading to a decrease in leptin effects to increase the activities of the autonomic nervous and cardiovascular systems.

Leptin resistance in obesity is characterized by decreased sensitivity to proopiomelanocortin products

Obesity in normal animals has been demonstrated to be associated with a decrease in sensitivity to leptin especially as it relates to leptins capacity to increase sympathetic nerve activity and enhance cardiovascular dynamics. In normal animals leptin has been demonstrated to exert significant regulatory responses by its capacity to increase proopiomelanocortin (POMC) expression and especially the increase in alpha melanocyte stimulating hormone (alphaMSH). These responses to leptin are blocked by a melanocortin-4 (MC-4) receptor antagonist. In this study we investigated the responsiveness of the sympathetic nervous system and cardiovascular system of high fat fed obese animals to the intracerebroventricular (ICV) administration of the POMC products alphaMSH and beta-endorphin (beta-END). We further investigated these responses in obese animals following leptin administration in the presence of MC-4 receptor and opioid receptor blockade. The ICV administration of leptin resulted in an increase in lumbar sympathetic nerve activity (LSNA) and mean arterial pressure (MAP) in normals but decreased it in the obese. The ICV administration of alphaMSH increased the LSNA and MAP in normal animals but to a lesser degree in obese animals. On the other hand beta-endorphin decreased the LSNA and MAP in normal animals but increased it in obese animals. Additionally ICV leptin administration in obese animals in the presence of MC-4 or opioid receptor blockade resulted in an increase in sympathetic activity and a pressor response. From these studies we conclude that obesity in high fat fed animals is characterized by a decreased sensitivity to alphaMSH and a paradoxical response to beta-endorphin and this altered responsiveness may be a factor in the altered leptin resistance characteristic of obese animals.

The Beneficial Effects α‐Cyclodextrin on Blood Lipids and Weight Loss in Healthy Humans

α‐Cyclodextrin (α‐CD) is a soluble fiber derived from corn. It has previously been reported that early intervention with Mirafit fbcx, a trademarked name for α‐CD, has beneficial effects on weight management in obese individuals with type 2 diabetes, and that it preferentially reduces blood levels of saturated and trans fats in the LDL receptor knockout mice. The current investigation involves overweight but not obese nondiabetic individuals and was intended to confirm the effects of α‐CD on both weight management and improving blood lipid levels. Forty‐one healthy adults (age: 41.4 ± 13.6 years) participated in this 2‐month, double‐blinded, crossover study. In 28 compliant participants (8 males and 20 females), when the active phase was compared to the control phase, there were significant decreases in body weight (−0.4 ± 0.2 kg, P < 0.05), serum total cholesterol (mean ± s.e.m., −0.295 ± 0.10 mmol/l, 5.3%, P < 0.02) and low‐density lipoprotein (LDL) cholesterol (−0.23 ± 0.11 mmol/l, −6.7%, P < 0.05). Apolipoprotein B (Apo B) (−0.0404 ± 0.02 g/l, −5.6%, P = 0.06) and insulin levels also decreased by 9.5% (−0.16 ± 0.08 pmol/l, P = 0.06) while blood glucose and leptin levels did not change. These results suggest that α‐CD exerts its beneficial health effects on body weight and blood lipid profile in healthy nonobese individuals, as previously reported in obese individuals with type 2 diabetes.

Poor Nutrient Intake and High Obese Rate in an Urban African American Population with Hypertension

Objective: To describe the nutrient intake patterns and general health conditions in an African American (AA) hypertensive population living in Detroit, MI. Methods: Demographic, anthropometric, general health condition and 3-day dietary recalls were collected from 387 AAs in community-based settings. Only data from 342 participants who met the inclusion criteria were reported. Results: The obesity and type 2 diabetes prevalence in this minority population were significantly higher, and both energy and nutrient intakes were significantly lower than the RDAs or those reported in NHANES. Female participants reported their highest weight at an earlier age but their body weight reduced in the older group. No such trend was observed in male participants. Both males and females consumed significantly fewer servings of fruit, vegetable and grains as recommended by USDA. As household income increased, the consumption of fruits and vegetables were also increased. Conclusion: In order to reduce the incidence of obesity and hypertension in this minority population, dietary intervention should begin at adolescence or even earlier. DASH diet would be beneficial for this population.

Perinatal n-3 fatty acid imbalance affects fatty acid composition in rat offspring.

This study was designed to investigate the effects of high and low n-3 FA feeding during perinatal period on the growth and FA profiles in the Wistar rat offspring. Female rats were randomized into three diet groups during pregnancy and lactation (L): Control (CON, ratio of n-3/n-6 approximately 0.14, n=24); n-3 FA deficient (LOW, ratio of n-3/n-6 approximately 0, n=31) and n-3 FA excess (HIGH, ratio of n-3/n-6 approximately 14.0, n=23). Milk samples were obtained on L14. After L24, all offspring were fed the control diet until killed at 23-25 weeks of age. There were no group differences in maternal weight gains or offspring birth weights. After birth, the HIGH offspring weighed the least while CON offspring the most. The FA profiles of the CON and LOW milk resembled CON diet, and the HIGH milk resembled HIGH diet. Body FA profiles of males from all groups were similar to the CON milk profile, but the CON and LOW females resembled the CON milk, while the HIGH females resembled the HIGH milk. All HIGH offspring had increased n-3 levels and n-3/n-6 ratios (males: 0.16+/-0.01; females: 0.23+/-0.06). Thus LOW dams likely had maternal body fat mobilization that compensated for the deficiency in dietary n-3 FA, while a compensatory mechanism was not observed when intake was high. Excess amount of n-3 FA affected female offspring more than males. These data indicate the long-lasting effects of supplementation and supplementing high amounts of n-3 FA during pregnancy and lactation may not be advisable.

Factors Associated with Weight Resilience in Obesogenic Environments in Female African-American Adolescents

This study used a descriptive, cross-sectional analysis to examine a social ecological model of obesity among African-American female adolescents residing in obesogenic environments. The goal was to identify factors that promote weight resilience, defined as maintaining a healthy body weight despite living in an environment that encourages inactivity and undermines healthy weight behaviors. During 2005 to 2008, weight-resilient (n=32) and obese (n=35) African-American female adolescents (12 to 17 years) living in Detroit, MI, and their caregivers completed measures of individual, family, and extrafamilial weight-resilience factors. Variables related to weight resilience in bivariate analyses were subjected to multivariate analysis using logistic regression to test the hypothesis that these factors independently predicted adolescent membership into the weight-resilient or obese group. As hypothesized, the odds of an adolescent being weight resilient were predicted by lower caregiver body mass index (calculated as kg/m(2)) (odds ratio [OR]=0.790; 95% confidence interval [CI]: 0.642 to 0.973), lower caregiver distress (OR=0.796; 95% CI: 0.635 to 0.998), higher caregiver monitoring and supervision of exercise (OR=5.746; 95% CI: 1.435 to 23.004), more frequent full-service grocery store shopping (OR=5.147; 95% CI: 1.137 to 23.298), and more peer support for eating (OR=0.656; 95% CI: 0.445 to 0.969). Contrary to prediction, lower eating self-efficacy (OR=0.597; 95% CI: 0.369 to 0.965) also predicted weight resilience. The model correctly classified 92.5% of all cases. Findings suggest that increasing psychosocial weight-resilience factors across multiple systems might be an important intervention strategy for obese African-American female adolescents residing in obesogenic environments.

The effect of CNS opioid on autonomic nervous and cardiovascular responses in diet-induced obese rats

The intracerebroventricular (i.c.v.) infusion of beta-endorphin can cause either a decrease in blood pressure in normal rats or an increase in obese rats. Diet-induced obesity is associated with an increase of hypothalamic mu opioid receptors. Since beta-endorphins act by opioid receptors, we investigated the effect of CNS mu as well as kappa opioid receptor agonist and antagonist on mean blood pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in male Wistar rats fed either a high fat (HF) (40% fat by weight) or a regular low fat (control) (4% fat by weight) diet. After a 12-week-feeding period the animals were implanted with i.c.v. cannulas and 3-5 days later they were anesthetized and instrumented to record MAP, HR and RSNA. HF rats have higher MAP and the i.c.v. injection of a mu opioid agonist (DAMGO) initially decreased the MAP and then increased MAP, HR and RSNA in the normal animals. The increase was greater in HF animals. The i.c.v. injection of the mu antagonist (beta-FNA) resulted in a significantly greater decrease in MAP in HF animals. beta-FNA increased the RSNA in the HF rats but decreased it in the normal rats. The kappa agonist (dynorphin) decreased MAP in normal rats followed by a return to baseline, but not in HF rats. The kappa antagonist, nor-binaltorphimine (N-BP), increased MAP and RSNA in normal rats and to a lesser extent in HF rats. These findings suggest that rats given a high fat diet have higher blood pressures and a greater mu opioid-mediated responsiveness with a greater mu opioid-mediated autonomic tone. Additionally there is a decreased kappa responsiveness and tone in the HF rats. Both these changes, increased mu and decreased kappa responsiveness could strongly contribute to the increased blood pressure in obese animals.

The Effect of α-Cyclodextrin on postprandial lipid and glycemic responses to a fat-containing meal

OBJECTIVE α-Cyclodextrin (α-CD), a soluble dietary fiber derived from corn, marketed under the trade name FBCx®, has the potential to help individuals manage their weight and improve their lipid profiles. Initial studies in healthy overweight and/or obese diabetic individuals found that, in those consuming a normal to high fat diet over a 4 or 12 week period, α-CD use was associated with weight loss or maintenance and a reduction in triglyceride (TG) and cholesterol levels in hyperlipidemic individuals. Furthermore, α-CD use was associated with the positive effects of increasing insulin and leptin sensitivities. To date, the immediate post-prandial glucose and lipid responses to a fat-containing meal have not been reported. MATERIALS/METHOD This double blinded placebo controlled cross-over trial examined the effect of 2 g of α-CD taken immediately following consumption of a commercially prepared high-fat breakfast meal on the acute postprandial responses in healthy adults. RESULTS The coincidental consumption of α-CD with a fat-containing meal was associated with a significant reduction in postprandial TG responses over time when compared to placebo. When incremental area under the curve was calculated, the area under the curve associated with α-CD consumption was significantly smaller than the Placebo area (0.30±1.07 mmol/L/3 h vs. 0.98±0.88 mmol/L/3 h, p<0.05). There were no significant changes in glucose or cholesterol levels. CONCLUSION α-Cyclodextrin was shown to significantly lower acute postprandial blood triglyceride levels.

Long-term effects of exogenous leptin on body weight and fat in post-obese female rats.

This study was designed to test the hypothesis that short-term leptin infusion during the post-obese refeeding phase of weight-reduced rats would reduce the rate of weight regain and, as a result, reduce the final body weight and fat content in weight-reduced rats. Ninety-six female Wistar rats were divided into four groups: (1) LFCON (low-fat control) group: Rats in this group were fed the control low-fat (LF) diet ad lib for the entire study period. (2) HFCON (high-fat control) group: Rats in this group were fed the high-fat (HF, 40% fat) diet ad lib for the study period. (3) HFRLP (high-fat fed, weight-reduced, leptin treatment) group: Obese rats in this group were weight-reduced and received leptin infusion for 2 weeks (miniosmotic pumps, 0.5 microg/kg/day) during the post-obese refeeding period. (4) HFRSM (high-fat fed, weight-reduced, sham control) group: Rats in this sham-control group were treated the same as the rats in the HFRLP group with the exception that no leptin was actually infused during the first 2 weeks of refeeding period. The results demonstrated that 2 weeks of leptin treatment during the early refeeding phase did not prevent weight regain in weight-reduced rats, but it significantly reduced body fat content in these rats as compared to ad lib fed obese control rats. One cycle of weight reduction and regain did not alter the body weight and body fat content in HFRSM rats when compared to obese control rats. Therefore, leptin treatment was effective in reducing body fat content in post-obese rats for up to 7 weeks, but the long-term effect of short-term leptin treatment needs to be further examined.