Jose A. Canas

Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity

A novel perspective of the function of carotenoids and carotenoid-derived products - including, but not restricted to, the retinoids - is emerging in recent years which connects these compounds to the control of adipocyte biology and body fat accumulation, with implications for the management of obesity, diabetes and cardiovascular disease. Cell and animal studies indicate that carotenoids and carotenoids derivatives can reduce adiposity and impact key aspects of adipose tissue biology including adipocyte differentiation, hypertrophy, capacity for fatty acid oxidation and thermogenesis (including browning of white adipose tissue) and secretory function. Epidemiological studies in humans associate higher dietary intakes and serum levels of carotenoids with decreased adiposity. Specifically designed human intervention studies, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. The objective of this review is to summarize recent findings in this area, place them in physiological contexts, and provide likely regulatory schemes whenever possible. The focus will be on the effects of carotenoids as nutritional regulators of adipose tissue biology and both animal and human studies, which support a role of carotenoids and retinoids in the prevention of abdominal adiposity.

Insulin Resistance and Adiposity in Relation to Serum β-Carotene Levels

OBJECTIVE To determine the effects of placebo vs an encapsulated supplement of fruit and vegetable juice concentrate (FVJC) on serum β-carotene levels, insulin resistance, adiposity, and subclinical inflammation in boys. STUDY DESIGN Thirty age-matched prepubertal boys (9 lean and 21 overweight (OW); age range, 6-10 years) were studied. All participants received nutrition counseling and were randomized to receive FVJC or placebo capsules for 6 months. Total cholesterol, triglycerides, lipid corrected β-carotene, serum retinol, glucose, insulin, retinol binding protein-4, leptin, adiponectin, leptin-to-adiponectin ratio, high-sensitivity C-reactive protein, and interleukin-6 were measured before and after the 6-month intervention. Homeostasis model assessment-insulin resistance (HOMA-IR), acute insulin response to intravenous glucose, along with abdominal fat mass (dual-energy x-ray absorptiometry) were also determined. RESULTS Baseline β-carotene concentrations correlated inversely with HOMA-IR, leptin-to-adiponectin ratio, and abdominal fat mass (P ≤ .01). FVJC intake increased β-carotene concentrations (P ≤ .001) but did not influence retinol or retinol binding protein-4. Retinol insufficiency <1.047 μM was present in 18% of the entire cohort at baseline and in 37% at 6 months. HOMA-IR decreased after supplementation in the OW cohort, when adjusted for percent weight change (P = .014). The percent change in abdominal fat mass increased in the placebo group and decreased in the FVJC group (P = .029). CONCLUSIONS A 6-month supplementation with FVJC in the presence of nutritional counseling was associated with an increase in serum β-carotene concentrations and a reduction in adiposity in conjunction with an improvement in insulin resistance in OW boys.

Biomarkers for cardiovascular risk in children.

Purpose of review The magnitude of lifetime risk of cardiovascular disease (CVD) has radically increased along with the high prevalence of obesity in children. The spotlight is now on dysfunctional adiposity as a precursor for the development of premature CVD. As full-blown CVD is not present in childhood, there is a critical need for surrogate markers to best assess, predict, and treat the children who are vulnerable to developing CVD. Recent findings Accumulation of excess fat mass can be conceived as a derangement in the balance between energy intake and expenditure. This appears to provoke various structural and metabolic alterations leading to adipocyte dysfunction, with important cardiovascular health consequences. Subclinical inflammation, insulin resistance, oxidative stress, and endothelial dysfunction appear to play important roles early in the clinical course of obesity. Summary Associations between biomarkers and noninvasive measures of early atherosclerosis in children continue to emerge and several biomarkers appear to be promising. At present, there are no explicit data to recommend any of these biomarkers as a routine clinical marker of CVD in children. More work is needed to validate these biomarkers and to improve understanding of their role in CVD risk prediction in the pediatric population.

A randomized, double blind, placebo-controlled pilot trial of the safety and efficacy of atorvastatin in children with elevated low-density lipoprotein cholesterol (LDL-C) and type 1 diabetes.

Children with type 1 diabetes (T1D) and elevated LDL‐C have an increased risk for cardiovascular disease, a process that can begin in childhood.

Serum Nutritional Biomarkers and Their Associations with Sleep among US Adults in Recent National Surveys

Background The associations between nutritional biomarkers and measures of sleep quantity and quality remain unclear. Methods Cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) 2005–2006 were used. We selected 2,459 adults aged 20–85, with complete data on key variables. Five sleep measures were constructed as primary outcomes: (A) Sleep duration; (B) Sleep disorder; (C) Three factors obtained from factor analysis of 15 items and labeled as “Poor sleep-related daytime dysfunction” (Factor 1), “Sleepiness” (Factor 2) and “Sleep disturbance” (Factor 3). Main exposures were serum concentrations of key nutrients, namely retinol, retinyl esters, carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene), folate, vitamin B-12, total homocysteine (tHcy), vitamin C, 25-hydroxyvitamin D (25(OH)D) and vitamin E. Main analyses consisted of multiple linear, logistic and multinomial logit models. Results Among key findings, independent inverse associations were found between serum vitamin B-12 and sleep duration, 25(OH)D and sleepiness (as well as insomnia), and between folate and sleep disturbance. Serum total carotenoids concentration was linked to higher odds of short sleep duration (i.e. 5–6 h per night) compared to normal sleep duration (7–8 h per night). Conclusions A few of the selected serum nutritional biomarkers were associated with sleep quantity and quality. Longitudinal studies are needed to ascertain temporality and assess putative causal relationships.

Carotenoids in Adipose Tissue Biology and Obesity

Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition.

Helicobacter pylori Seropositivity’s Association with Markers of Iron, 1-Carbon Metabolism, and Antioxidant Status among US Adults: A Structural Equations Modeling Approach

Objectives We tested a model in which Helicobacter pylori seropositivity (Hps) predicted iron status, which in turn acted as a predictor for markers of 1-C metabolism that were then allowed to predict antioxidant status. Methods National Health and Nutrition Examination Surveys (NHANES 1999–2000) cross-sectional data among adults aged 20–85 y were analyzed (n = 3,055). Markers of Hps, iron status (serum ferritin and transferrin saturation (TS)); 1-C metabolism (serum folate (FOLserum), B-12, total homocysteine (tHcy), methylmalonic acid (MMA)) and antioxidant status (vitamins A and E) were entered into a structural equations model (SEM). Results Predictors of Hps included older age, lower education and income, racial/ethnic groups (lowest among Non-Hispanic Whites), and lifetime cigarette smoking. SEM modeling indicated that Hps had a direct inverse relationship with iron status (combining serum ferritin and TS) which in turn was positively related to 1-C metabolites (higher serum folate, B-12 or lower tHcy/MMA) that were positively associated with antioxidant status (combining serum vitamins A and E). Another pathway that was found bypassed 1-C metabolites (Hps → Iron_st → Antiox). The sum of all indirect effects from Hps combining both pathways and the other indirect pathways in the model (Hps → Iron_st → OneCarbon; Hps →OneCarbon →Antiox) was estimated at β = -0.006±0.003, p<0.05. Conclusions In sum, of the total effect of H. pylori seropositivity on antioxidant status, two significant indirect pathways through Iron status and 1-Carbon metabolites were found. Randomized controlled trials should be conducted to uncover the concomitant causal effect of H. pylori eradication on improving iron status, folate, B-12 and antioxidant status among H. pylori seropositive individuals.

Fatty acid binding proteins 4 and 5 in overweight prepubertal boys: effect of nutritional counselling and supplementation with an encapsulated fruit and vegetable juice concentrate

Elevated fatty acid binding proteins (FABP) may play a role in obesity and co-morbidities. The role of nutritional interventions in modulating these levels remains unclear. The aim of this post hoc study was to determine the effect of overweight (OW) on FABP4 and FABP5 in boys in relation to indices of adiposity, insulin resistance and inflammation, and to investigate the effects of a 6-month supplementation with an encapsulated fruit and vegetable juice concentrate (FVJC) plus nutritional counselling (NC) on FABP levels. A post hoc analysis of a double-blind, randomised, placebo-controlled study of children recruited from the general paediatric population was performed. A total of thirty age-matched prepubertal boys (nine lean and twenty-one OW; aged 6–10 years) were studied. Patients received NC by a registered dietitian and were randomised to FVJC or placebo capsules for 6 months. FABP4, FABP5, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), glucose-induced acute insulin response (AIR), lipid-corrected β-carotene (LCβC), adiponectin, leptin, high-sensitivity C-reactive protein (hs-CRP), IL-6 and body composition by dual-energy X-ray absorptiometry were determined before and after the intervention. FABP were higher (P < 0·01) in the OW v. lean boys and correlated directly with HOMA-IR, abdominal fat mass (AFM), hs-CRP, IL-6, and LCβC (P < 0·05 for all). FABP4 was associated with adiponectin and AIR (P < 0·05). FVJC plus NC reduced FABP4, HOMA-IR and AFM (P < 0·05 for all) but not FABP5. OW boys showed elevated FABP4 and FABP5, but only FABP4 was lowered by the FVJC supplement.

Magnetic resonance imaging measures of decreased aortic strain and distensibility are proportionate to insulin resistance in adolescents with type 1 diabetes mellitus

To determine whether children with type 1 diabetes mellitus (T1DM) have evidence of increased aortic stiffness or early atherosclerosis as measured by magnetic resonance imaging (MRI).

Interventions to reduce cardiovascular risk in children with type 1 diabetes.

BACKGROUND Despite recent advances in improved glycemic control, the magnitude of lifetime risk from premature cardiovascular disease in individuals with type 1 diabetes remains at least 10 fold higher than in the general population. The availability of lipoprotein fractionation has allowed the spotlight for this increased risk to shift from dysglycemia to diabetes-induced dyslipidemia associated with insulin resistance. Interventions designed to simultaneously improve both factors can have distinct and additive effects on slowing the initiation and progression of atherosclerotic lesions. As fullblown cardiovascular disease is not evident during childhood, there is a critical need to identify the most predictable surrogate markers that could assign elevated risk, as well as the design of safe and targeted interventions that could improve outcomes in this population. CONCLUSION This review will examine the evidence supporting the notion that cardiovascular disease in type 1 diabetes is associated with significant insulin resistance and it begins in childhood, making it necessary to design rational clinical trials that will significantly reduce risk in this population.