Elaine Souza

Dairy Foods in a Moderate Energy Restricted Diet Do Not Enhance Central Fat, Weight, and Intra-Abdominal Adipose Tissue Losses nor Reduce Adipocyte Size or Inflammatory Markers in Overweight and Obese Adults: A Controlled Feeding Study.

Background. Research on dairy foods to enhance weight and fat loss when incorporated into a modest weight loss diet has had mixed results. Objective. A 15-week controlled feeding study to determine if dairy foods enhance central fat and weight loss when incorporated in a modest energy restricted diet of overweight and obese adults. Design. A 3-week run-in to establish energy needs; a 12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and obese adults randomly assigned to diets: ≤1 serving dairy/d (low dairy, LD) or ≤4 servings dairy/d (adequate dairy, AD). All foods were weighed and provided by the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT), subcutaneous adipose tissue (SAT) macrophage number, SAT inflammatory gene expression, and circulating cytokines were measured. Results. No diet differences were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There was a significant increase (P = 0.02) in serum 25-hydroxyvitamin D in the AD group. Conclusion. Whether increased dairy intake during weight loss results in greater weight and fat loss for individuals with metabolic syndrome deserves investigation. Assessment of appetite, hunger, and satiety with followup on weight regain should be considered.

Improved Metabolic Health Alters Host Metabolism in Parallel with Changes in Systemic Xeno-Metabolites of Gut Origin

Novel plasma metabolite patterns reflective of improved metabolic health (insulin sensitivity, fitness, reduced body weight) were identified before and after a 14–17 wk weight loss and exercise intervention in sedentary, obese insulin-resistant women. To control for potential confounding effects of diet- or microbiome-derived molecules on the systemic metabolome, sampling was during a tightly-controlled feeding test week paradigm. Pairwise and multivariate analysis revealed intervention- and insulin-sensitivity associated: (1) Changes in plasma xeno-metabolites (“non-self” metabolites of dietary or gut microbial origin) following an oral glucose tolerance test (e.g. higher post-OGTT propane-1,2,3-tricarboxylate [tricarballylic acid]) or in the overnight-fasted state (e.g., lower γ-tocopherol); (2) Increased indices of saturated very long chain fatty acid elongation capacity; (3) Increased post-OGTT α-ketoglutaric acid (α-KG), fasting α-KG inversely correlated with Matsuda index, and altered patterns of malate, pyruvate and glutamine hypothesized to stem from improved mitochondrial efficiency and more robust oxidation of glucose. The results support a working model in which improved metabolic health modifies host metabolism in parallel with altering systemic exposure to xeno-metabolites. This highlights that interpretations regarding the origins of peripheral blood or urinary “signatures” of insulin resistance and metabolic health must consider the potentially important contribution of gut-derived metabolites toward the hosts metabolome.

Association between Subcutaneous White Adipose Tissue and Serum 25-Hydroxyvitamin D in Overweight and Obese Adults

Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons enrolled in a twelve week energy restricted diet. Baseline and post-intervention gluteal SWAT biopsies were collected from 20 subjects participating in a larger clinical weight loss intervention. LC-MS/MS was utilized to determine SWAT 25(OH)D concentrations. Serum 25(OH)D and 1,25(OH)2D were measured by RIA. Body composition was assessed by dual energy x-ray absorptiometry. SWAT 25(OH)D concentrations were 5.8 ± 2.6 nmol/kg tissue and 6.2 ± 2.7 nmol/kg tissue pre- and post-intervention SWAT, respectively. There was a significant positive association between SWAT 25(OH)D concentration and serum 25(OH)D concentration (r = 0.52, P < 0.01). Both SWAT and serum 25(OH)D concentrations did not significantly change after a twelve-week period of energy restriction with approximately 5 kg of fat loss. In conclusion, we have demonstrated our LC-MS/MS method can detect 25(OH)D3 in human subcutaneous fat tissue from overweight and obese individuals and is consistent with previously reported concentrations in swine. Additionally, our findings of no significant changes in SWAT 25(OH)D3 or serum 25(OH)D after a 6% loss of total body weight and 13% reduction in total fat provides the first human evidence that adipose 25(OH)D does not likely contribute to serum 25(OH)D with moderate weight loss; whether this is also the case with larger amounts of weight loss is unknown. Weight loss alone is not sufficient to increase serum 25(OH)D and increases in dietary or dermal biosynthesis of vitamin D appear to be the most critical contributors to in vitamin D status.

Associations among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss

INTRODUCTION Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE Our aims were to (1) determine if adequate dairy intake attenuates weight loss-induced bone loss; (2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; and (3) model the contribution of these variables to post weight-loss BMD and BMC. METHODS Overweight/obese women (BMI: 28-37 kg/m2) were enrolled in an energy reduced (-500 kcal/d; -2092 kJ/d) diet with adequate dairy (AD: 3-4 servings/d; n=25, 32.2±8.8 years) or low dairy (LD: ≤1 serving/d; n=26, 31.7±8.4 years). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. RESULTS Following weight loss, AD intake resulted in significantly greater (p=0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post-body fat was negatively associated with hip and lumbar spine BMC (r=-0.28, p=0.04 to -0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = -0.29 (p=0.04) to r = -0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss factors. Pre-weight loss factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the factors contributed to the variance in lumbar spine BMD. CONCLUSION AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone and inflammatory markers suggesting that inflammation suppresses bone metabolism. Using factor analysis, 19.6% of total variance in post-weight loss hip BMD could be explained by endocrine, immune, and anthropometric variables, but not lumbar spine BMD.

Acylcarnitines as markers of exercise‐associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons

What is the central question of this study? Does improved metabolic health and insulin sensitivity following a weight‐loss and fitness intervention in sedentary, obese women alter exercise‐associated fuel metabolism and incomplete mitochondrial fatty acid oxidation (FAO), as tracked by blood acylcarnitine patterns? What is the main finding and its importance? Despite improved fitness and blood sugar control, indices of incomplete mitochondrial FAO increased in a similar manner in response to a fixed load acute exercise bout; this indicates that intramitochondrial muscle FAO is inherently inefficient and is tethered directly to ATP turnover.

Increased cytokine production by monocytes from human subjects who consumed grape powder was not mediated by differences in dietary intake patterns

Recently, in a randomized, double-blind crossover study, we reported that consumption of grape powder by obese human subjects increased the production of the proinflammatory cytokines interleukin (IL)-1β and IL-6 by peripheral blood monocytes after ex vivo stimulation with bacterial lipopolysaccharide compared with the placebo treatment. We hypothesized that dietary grape powder increased the production of these cytokines by stimulated monocytes. To test this hypothesis, we used 24-hour dietary recall data to determine if differences in dietary patterns played a role in increased cytokine production. No differences in total energy, protein, carbohydrates, or fat intake in the diets were observed between the grape powder and placebo intervention periods. There were no differences observed in consumption of meats and poultry, eggs, fish, vegetables, grains, total dairy, or nuts and seeds by the participants between the 2 intervention periods. When participants received the grape powder, the recall data showed decreased intakes of butyric and capric acids (P<.05), and a possible trend toward decreased intake of cheese and total fruit (P<.1). Positive associations between the intakes of margaric acid, butter, total dairy, or whole grain and IL-6 production were observed (P<.05). However, path analysis showed that total energy, protein, carbohydrates, and fats, and individual fatty acids did not influence the production of cytokines by monocytes. The path analysis indicated that the increased cytokine production by lipopolysaccharide-stimulated monocytes from obese human subjects was caused by the grape powder and not mediated by differences in dietary intake.