Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease

Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease 

[Cardiovascular disease risk]

from American Journal of Clinical Nutrition current issue by Monagas, M., Khan, N., Andres-Lacueva, C., Casas, R., Urpi-Sarda, M., Llorach, R., Lamuela-Raventos, R. M., Estruch, R.

Background: Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease. Because atherosclerosis is considered a low-grade inflammatory disease, some feeding trials have analyzed the effects of cocoa (an important source of flavonoids) on inflammatory biomarkers, but the results have been controversial.

Objective: The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients.

Design: Forty-two high-risk volunteers (19 men and 23 women; mean ± SD age: 69.7 ± 11.5 y) were included in a randomized crossover feeding trial. All subjects received 40 g cocoa powder with 500 mL skim milk/d (C+M) or only 500 mL skim milk/d (M) for 4 wk. Before and after each intervention period, cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated.

Results: Adherence to the dietary protocol was excellent. No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups. However, in monocytes, the expression of VLA-4, CD40, and CD36 was significantly lower (P = 0.005, 0.028, and 0.001, respectively) after C+M intake than after M intake. In addition, serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower (both P = 0.007) after C+M intake than after M intake.

Conclusions: These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease. These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis.

Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults

Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults 

[Obesity and eating disorders]

from American Journal of Clinical Nutrition current issue by Varady, K. A, Bhutani, S., Church, E. C, Klempel, M. C

Background: The ability of modified alternate-day fasting (ADF; ie, consuming 25% of energy needs on the fast day and ad libitum food intake on the following day) to facilitate weight loss and lower vascular disease risk in obese individuals remains unknown.

Objective: This study examined the effects of ADF that is administered under controlled compared with self-implemented conditions on body weight and coronary artery disease (CAD) risk indicators in obese adults.

Design: Sixteen obese subjects (12 women, 4 men) completed a 10-wk trial, which consisted of 3 phases: 1) a 2-wk control phase, 2) a 4-wk weight loss/ADF controlled food intake phase, and 3) a 4-wk weight loss/ADF self-selected food intake phase.

Results: Dietary adherence remained high throughout the controlled food intake phase (days adherent: 86%) and the self-selected food intake phase (days adherent: 89%). The rate of weight loss remained constant during controlled food intake (0.67 ± 0.1 kg/wk) and self-selected food intake phases (0.68 ± 0.1 kg/wk). Body weight decreased (P < 0.001) by 5.6 ± 1.0 kg (5.8 ± 1.1%) after 8 wk of diet. Percentage body fat decreased (P < 0.01) from 45 ± 2% to 42 ± 2%. Total cholesterol, LDL cholesterol, and triacylglycerol concentrations decreased (P < 0.01) by 21 ± 4%, 25 ± 10%, and 32 ± 6%, respectively, after 8 wk of ADF, whereas HDL cholesterol remained unchanged. Systolic blood pressure decreased (P < 0.05) from 124 ± 5 to 116 ± 3 mm Hg.

Conclusion: These findings suggest that ADF is a viable diet option to help obese individuals lose weight and decrease CAD risk. This trial was registered at clinicaltrials.gov as UIC-004-2009.

Circadian Timing of Food Intake Contributes to Weight Gain

Circadian Timing of Food Intake Contributes to Weight Gain

Deanna M. Arble1, Joseph Bass1,2, Aaron D. Laposky1, Martha H. Vitaterna1 and Fred W. Turek1

Abstract

Studies of body weight regulation have focused almost entirely on caloric intake and energy expenditure. However, a number of recent studies in animals linking energy regulation and the circadian clock at the molecular, physiological, and behavioral levels raise the possibility that the timing of food intake itself may play a significant role in weight gain. The present study focused on the role of the circadian phase of food consumption in weight gain. We provide evidence that nocturnal mice fed a high-fat diet only during the 12-h light phase gain significantly more weight than mice fed only during the 12-h dark phase. A better understanding of the role of the circadian system for weight gain could have important implications for developing new therapeutic strategies for combating the obesity epidemic facing the human population today.

A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss

A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss

by Badman, M. K., Kennedy, A. R., Adams, A. C., Pissios, P., Maratos-Flier, E.

In mice of normal weight and with diet-induced obesity, a high-fat, low-carbohydrate ketogenic diet (KD) causes weight loss, reduced circulating glucose and lipids, and dramatic changes in hepatic gene expression. Many of the effects of KD are mediated by fibroblast growth factor 21 (FGF21). We tested the effects of KD feeding on ob/ob mice to determine if metabolic effects would occur in obesity secondarily to leptin deficiency. We evaluated the effect of prolonged KD feeding on weight, energy homeostasis, circulating metabolites, glucose homeostasis, and gene expression. Subsequently, we evaluated the effects of leptin and fasting on FGF21 expression in ob/ob mice. KD feeding of ob/ob mice normalized fasting glycemia and substantially reduced insulin and lipid levels in the absence of weight loss. KD feeding was associated with significant increases in lipid oxidative genes and reduced expression of lipid synthetic genes, including stearoyl-coenzyme A desaturase 1, but no change in expression of inflammatory markers. In chow-fed ob/ob mice, FGF21 mRNA was elevated 10-fold compared with wild-type animals, and no increase from this elevated baseline was seen with KD feeding. Administration of leptin to chow-fed ob/ob mice led to a 24-fold induction of FGF21. Fasting also induced hepatic FGF21 in ob/ob mice. Thus, KD feeding improved ob/ob mouse glucose homeostasis without weight loss or altered caloric intake. These data demonstrate that manipulation of dietary macronutrient composition can lead to marked improvements in metabolic profile of leptin-deficient obese mice in the absence of weight loss.

Inflammation and impaired adipogenesis in hypertrophic obesity in man

Inflammation and impaired adipogenesis in hypertrophic obesity in man

by Gustafson, B., Gogg, S., Hedjazifar, S., Jenndahl, L., Hammarstedt, A., Smith, U.

Obesity is associated mainly with adipose cell enlargement in adult man (hypertrophic obesity), whereas the formation of new fat cells (hyperplastic obesity) predominates in the prepubertal age. Adipose cell size, independent of body mass index, is negatively correlated with whole body insulin sensitivity. Here, we review recent findings linking hypertrophic obesity with inflammation and a dysregulated adipose tissue, including local cellular insulin resistance with reduced IRS-1 and GLUT4 protein content. In addition, the number of preadipocytes in the abdominal subcutaneous adipose tissue capable of undergoing differentiation to adipose cells is reduced in hypertrophic obesity. This is likely to promote ectopic lipid accumulation, a well-known finding in these individuals and one that promotes insulin resistance and cardiometabolic risk. We also review recent results showing that TNF, but not MCP-1, resistin, or IL-6, completely prevents normal adipogenesis in preadipocytes, activates Wnt signaling, and induces a macrophage-like phenotype in the preadipocytes. In fact, activated preadipocytes, rather than macrophages, may completely account for the increased release of chemokines and cytokines by the adipose tissue in obesity. Understanding the molecular mechanisms for the impaired preadipocyte differentiation in the subcutaneous adipose tissue in hypertrophic obesity is a priority since it may lead to new ways of treating obesity and its associated metabolic complications.

The origin of intermuscular adipose tissue and its pathophysiological implications

The origin of intermuscular adipose tissue and its pathophysiological implications

by Vettor, R., Milan, G., Franzin, C., Sanna, M., De Coppi, P., Rizzuto, R., Federspil, G.

The intermuscular adipose tissue (IMAT) is a depot of adipocytes located between muscle bundles. Several investigations have recently been carried out to define the phenotype, the functional characteristics, and the origin of the adipocytes present in this depot. Among the different mechanisms that could be responsible for the accumulation of fat in this site, the dysdifferentiation of muscle-derived stem cells or other mesenchymal progenitors has been postulated, turning them into cells with an adipocyte phenotype. In particular, muscle satellite cells (SCs), a heterogeneous stem cell population characterized by plasticity and self-renewal that allow muscular growth and regeneration, can acquire features of adipocytes, including the abilities to express adipocyte-specific genes and accumulate lipids. Failure to express the transcription factors that direct mesenchymal precursors into fully differentiated functionally specialized cells may be responsible for their phenotypic switch into the adipogenic lineage. We proved that human SCs also possess a clear adipogenic potential that could explain the presence of mature adipocytes within skeletal muscle. This occurs under some pathological conditions (i.e., primary myodystrophies, obesity, hyperglycemia, high plasma free fatty acids, hypoxia, etc.) or as a consequence of thiazolidinedione treatment or simply because of a sedentary lifestyle or during aging. Several pathways and factors (PPARs, WNT growth factors, myokines, GEF-GAP-Rho, p66shc, mitochondrial ROS production, PKCß) could be implicated in the adipogenic conversion of SCs. The understanding of the molecular pathways that regulate muscle-to-fat conversion and SC behavior could explain the increase in IMAT depots that characterize many metabolic diseases and age-related sarcopenia.

Transdifferentiation properties of adipocytes in the adipose organ

Transdifferentiation properties of adipocytes in the adipose organ

by Cinti, S.

Mammals have two types of adipocytes, white and brown, but their anatomy and physiology is different. White adipocytes store lipids, and brown adipocytes burn them to produce heat. Previous descriptions implied their localization in distinct sites, but we demonstrated that they are mixed in many depots, raising the concept of adipose organ. We explain the reason for their cohabitation with the hypothesis of reversible physiological transdifferentiation; they are able to convert one into each other. If needed, the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ associates with resistance to obesity and related disorders. Another example of physiological transdifferetiation of adipocytes is offered by the mammary gland; the pregnancy hormonal stimuli seems to trigger a reversible transdifferentiation of adipocytes into milk-secreting epithelial glands. The obese adipose organ is infiltrated by macrophages inducing chronic inflamation that is widely considered as a causative factor for insulin resistance. We showed that the vast majority of macrophages infiltrating the obese organ are arranged around dead adipocytes, forming characteristic crown-like structures. We recently found that visceral fat is more infiltrated than the subcutaneous fat despite a smaller size of visceral adipocytes. This suggests a different susceptibility of visceral and subcutaneous adipocytes to death, raising the concept of smaller critical death size that could be important to explain the key role of visceral fat for the metabolic disorders associated with obesity.

Exercise Training and Dietary Glycemic Load May Have Synergistic Effects on Insulin Resistance in Older Obese Adults

Exercise Training and Dietary Glycemic Load May Have Synergistic Effects on Insulin Resistance in Older Obese Adults

John P. Kirwana-d, Hope Barkoukisd, Latina M. Brooksa, b, Christine M. Marchettie, Bradley P. Stetzere, Frank Gonzalezf

  Abstract

Background/Aims: The aim of this study was to assess the combined effects of exercise and dietary glycemic load on insulin resistance in older obese adults. Methods: Eleven men and women (62 ± 2 years; 97.6 ± 4.8 kg; body mass index 33.2 ± 2.0) participated in a 12-week supervised exercise program, 5 days/week, for about 1 h/day, at 80-85% of maximum heart rate. Dietary glycemic load was calculated from dietary intake records. Insulin resistance was determined using the euglycemic (5.0 mM) hyperinsulinemic (40 mU/m2/min) clamp. Results: The intervention improved insulin sensitivity (2.37 ± 0.37 to 3.28 ± 0.52 mg/kg/min, p < 0.004), increased VO2max (p < 0.009), and decreased body weight (p < 0.009). Despite similar caloric intakes (1,816 ± 128 vs. 1,610 ± 100 kcal/day), dietary glycemic load trended towards a decrease during the study (140 ± 10 g before, vs. 115 ± 8 g during, p < 0.04). The change in insulin sensitivity correlated with the change in glycemic load (r = 0.84, p < 0.009). Four subjects reduced their glycemic load by 61 ± 8%, and had significantly greater increases in insulin sensitivity (78 ± 11 vs. 23 ± 8%, p < 0.003), and decreases in body weight (p < 0.004) and plasma triglycerides (p < 0.04) compared to the rest of the group. Conclusion: The data suggest that combining a low-glycemic diet with exercise may provide an alternative and more effective treatment for insulin resistance in older obese adults.

Effects of apple juice on risk factors of lipid profile, inflammation and coagulation, endothelial markers and atherosclerothic lesions in highcholesterolemic rabbits

Effects of apple juice on risk factors of lipid profile, inflammation and coagulation, endothelial markers and atherosclerothic lesions in highcholesterolemic rabbits

by Nafiseh Esmaeil

Background: Atherosclerosis which results from gradual deposition of lipids in medium and large arteries is a leading cause of mortality worldwide. The objective of this study was to determine the effect of apple juice on some risk factors of atherosclerosis and on the development of atherosclerosis in rabbits fed a high-cholesterol diet. Methods: Thirty two male rabbits were randomly divided into four groups: normal diet, high cholesterol diet (%1 cholesterol), 1 % cholesterol supplemented with 5ml apple juice(low dose) and 1 % cholesterol supplemented with 10ml apple juice (high dose) for 2 month. The C-reactive protein (CRP), nitrite, nitrate, fibrinogen,total cholesterol(TC) and factor VII were measured before the experiment and by the end of period. At the end ofstudy, fatty streak formation in right and left coronary arteries were determined using Chekanov method in all groups. Results: Both doses of apple juice significantly were decreased TC, TG, CRP, fibrinogen, factor VII levels, atherosclerotic lesion in right and left coronary arteries and increased nitrite and nitrate compared to cholesterolemic diet.Also using 10ml apple juice caused significant reduce in LDL-C and increase HDL-C , but 5 ml apple juice did not change these factors. Significant differences were observed between 5 and 10ml apple juice groups by LDL-C. No significant difference was found between 5 and 10 ml apple juice groups with regard to CRP, nitrite, nitrate, fibrinogen, factor VII, TG, HDL-C and TC concentrations. Conclusion: Apple juice can effectively prevent the progress of atherosclerosis.This is likely due to antioxidant and anti-inflammatory effect of apple juice.