Sylvia Santosa

Why are we shaped differently and why does it matter

Body fat distribution is an important predictor of metabolic abnormalities in obese humans. Dysregulation of free fatty acid (FFA) release, especially from upper body subcutaneous adipose tissue, appears to contribute substantially to these metabolic disturbances. Why different individuals preferentially store fat in upper vs. lower body subcutaneous fat or subcutaneous vs. visceral fat is not completely understood. Current evidence suggests that defects in regional lipolysis are not the cause of net fat retention in larger fat depots. Regional variations in the storage of fatty acids, both meal derived and direct reuptake, and storage of circulating FFAs that may help to explain why some depots expand at the expense of others have been reported. We review the quantitative data on regional lipolysis, meal, and FFA storage in adults to provide an overview of fat balance differences in adults with different fat distribution patterns.

An Investigation of Hormone and Lipid Associations after Weight Loss in Women

Objective: The objectives of this study were to determine 1) whether the extent of weight loss is predictive of the degree of changes in hormone and lipid levels; 2) the interactions between energy regulating hormones after weight loss through an energy deficit/exercise protocol diet and exercise; 3) whether initial metabolic parameters are indicative of the extent of weight loss. Methods: Thirty-five hyperlipidemic females (BMI 28–39 kg/m2) 35–60 years old participated in a six month weight loss trial. Weight loss resulted from a diet and exercise program that when combined produced a 30% energy deficit. Fasting plasma taken during 2 wk stabilization periods at the beginning and end of the study was analysed for lipids, hormone and glucose levels. Results: Average weight loss was 11.7 ± 2.5 kg (p < 0.0001). TC, LDL-C, and triacylglycerols decreased 9.3 ± 9.5% (p < 0.0001), 7.4 ± 12.2% (p < 0.001), and 26.8 ± 19.6% (p < 0.05), respectively, while HDL-C increased (p < 0.05) by 8.2 ± 16.3%. Leptin levels declined (p < 0.001) 48.9 ± 16.0% and ghrelin levels rose (p < 0.001) 21.2 ± 26.7%. While overall levels of adiponectin did not differ, individual values changed such that weight loss predicted increases in adiponectin levels. Though initial weight did not predict weight loss, baseline lipid and insulin levels positively predicted weight loss. Conclusion: Initial metabolic parameters may be predictors of weight loss. Beneficial effects of weight loss as achieved through diet and exercise on measured parameters indicate moderate weight loss reduces key risk factors of cardiovascular disease in overweight individuals.

The Sexual Dimorphism of Lipid Kinetics in Humans.

In addition to the obvious differences in body shape, there are substantial differences in lipid metabolism between men and women. These differences include how dietary fatty acids are handled, the secretion and clearance of very low-density lipoprotein-triglycerides, the release rates of free fatty acids (FFA) from adipose tissue relative to energy needs, and the removal of FFA from the circulation, including the storage of FFA into adipose tissue via the direct uptake process. We will review what is known about these processes and how they may contribute to the sexual dimorphism of body fat distribution.

Adipocyte Fatty Acid Storage Factors Enhance Subcutaneous Fat Storage in Postmenopausal Women

Increases in weight have been associated with corresponding increases in insulin resistance in postmenopausal women. Although estrogen has significant impact on body fat and body fat distribution, the cellular mechanisms that influence this process are not yet known. We measured adipose tissue fatty acid (FA) storage and FA storage factors in 12 premenopausal and 11 postmenopausal women matched for age and body composition. Postmenopausal women had lower postprandial FA oxidation (indirect calorimetry), greater meal FA, and direct free FA (FFA) storage than premenopausal women, including two-fold greater meal FA storage in the femoral depot. The fed/fasted activities of adipose tissue lipoprotein lipase were not significantly different between premenopausal and postmenopausal women. In contrast, adipocyte acyl-CoA synthetase and diacylglycerol acyltransferase activities in postmenopausal women were significantly upregulated and were positively correlated with direct FFA storage rates. These findings suggest that the propensity for subcutaneous adipose tissue FA storage is increased in postmenopausal women, more so from changes in adipocyte FA storage factors than from adipose tissue lipoprotein lipase activity. Our results suggest that female sex steroids, most likely estrogen, have important effects on adipose tissue FA storage and FA oxidation that could promote fat gain in postmenopausal women.

Effects of Male Hypogonadism on Regional Adipose Tissue Fatty Acid Storage and Lipogenic Proteins

Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [3H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-13C]palmitate and [1-14C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans.

Oxidative stress in ocular disease: Does lutein play a protective role?

Although age-related macular degeneration and cataracts are leading causes of blindness, how they themselves are caused is unclear. These diseases are thought to result from damage caused, photochemically and nonphotochemically, to various cell types in the eye by oxidative stress. Because its

Adipose tissue fatty acid storage factors: effects of depot, sex and fat cell size.

Background/objectives:Patterns of postabsorptive adipose tissue fatty acid storage correlate with sex-specific body fat distribution. Some proteins and enzymes participating in this pathway include CD36 (facilitated transport), acyl-CoA synthetase (ACS; the first step in fat metabolism) and diacylglycerol acetyltransferase (DGAT; the final step of triglyceride synthesis). Our aim was to better define CD36, ACS and DGAT in relation to sex, subcutaneous fat depots and adipocyte size.Subjects/methods:Data were collected from studies conducted at Mayo Clinic between 2004 and 2012. Abdominal and femoral subcutaneous fat biopsy samples must have been collected in the postabsorptive state from healthy males and premenopausal females. Body composition was measured with dual-energy X-ray absorptiometry and abdominal computerized tomography scans. Adipocyte size (microscopy), CD36 protein content (enzyme-linked immunosorbent assay) and ACS and DGAT enzyme activities were measured. Data are presented as medians and 25th, 75th quartiles.Results:Males (n=60) and females (n=78) did not differ by age (37; 28, 46 years), body mass index (28.4; 24.6, 32.1 kg m−2) or abdominal (0.60; 0.45, 0.83 μg lipid per cell) and femoral adipocyte size (0.76; 0.60, 0.94 μg lipid per cell). Femoral ACS and DGAT were greater in females than males when expressed per mg lipid (ACS: 73 vs 55 pmol/mg lipid/min; DGAT: 5.5 vs 4.0 pmol/mg lipid/min; P<0.0001 for both) and per 1000 adipocytes (ACS: 59 vs 39 pmol per min per 1000 adipocytes; DGAT: 4.3 vs 3.1 pmol per min per 1000 adipocytes; P⩽0.0003 for both). There were no differences in abdominal fat storage factors between sexes. ACS and DGAT decreased as a function of adipocyte size (P<0.0001 for both). The decrease in ACS was greater in males and abdominal subcutaneous fat. There were no sex differences in CD36 in either fat depot, nor did it vary across adipocyte size.Conclusions:Facilitated transport of fatty acids by CD36 under postabsorptive conditions would not be different in those with large vs small adipocytes in either depot of both sexes. However, intracellular trafficking of fatty acids to triglyceride storage by ACS and DGAT may be less efficient in larger adipocytes.

Sex and sex steroids: impact on the kinetics of fatty acids underlying body shape

Abstract Adult humans have a remarkable sexual dimorphism in body shape. Men tend to store relatively more fat in the upper body whereas women store more fat in the lower body. We do not have a complete understanding of the mechanisms underlying these differences, but we know that people who preferentially store abdominal fat are at greater risk of metabolic disease. It is also known that the changes in sex steroid concentrations during puberty and again with advancing age are accompanied by changes in body fat distribution. The objective of this review is to describe what has been learned regarding the mechanisms underlying changes in regional body fat distribution that occur as a result of changes in sex hormones and to delineate effects of sex steroids in modulating body composition.

Cholesterol metabolism and body composition in women: the effects of moderate weight loss

Objective:To determine how moderate weight loss protocol through diet and exercise may affect changes in body composition, to determine the effects of weight loss on cholesterol metabolism and to examine the relationship between cholesterol metabolism and changes in body composition.Design:Thirty-five otherwise healthy, hypercholesterolemic women completed a 24-week weight loss study. A 20% decrease in energy intake through diet and a 10% increase in energy expenditure by exercise were combined with motivational strategies to encourage weight loss. The diet was self-selected and comprised of 50–60% carbohydrates, 20% protein and <30% fat.Results:Participants lost an average of 11.7±2.5 kg (P<0.001). Whole body and regional losses in tissue mass occurred after weight loss. After weight loss, cholesterol fractional synthesis rate (FSR) decreased (P=0.003) 3.86±9.33%, whereas rates of cholesterol absorption and turnover did not change (3.31±19.4%, P=0.32 and −0.01±6.20%, P=0.75, respectively). Changes in cholesterol turnover were positively correlated (r=0.44, P=0.01) with changes in FSR. Reductions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were predictive (β=−5.04, r=0.38; P=0.03, and β=−147, r=0.40; P=0.03, respectively) of increases in cholesterol turnover. Losses in skeletal muscle (SM) and upper-body SM predicted (β=6.82, r=0.36; P=0.04 and β=14.7, r=0.41; P=0.01, respectively) decreases in cholesterol absorption.Conclusions:Decreases in cholesterol synthesis after moderate weight loss are not compensated for by changes in cholesterol absorption or turnover. Changes in regional body composition were associated with variations in cholesterol metabolism. Understanding how weight loss affects cholesterol metabolism will help identify more effective treatment routes for overweight individuals undergoing weight loss resulting in earlier and more intensive therapy for the associated dyslipidemia.

From neutrophils to macrophages: differences in regional adipose tissue depots

Currently, we do not fully understand the underlying mechanisms of how regional adiposity promotes metabolic dysregulation. As adipose tissue expands, there is an increase in chronic systemic low‐grade inflammation due to greater infiltration of immune cells and production of cytokines. This chronic inflammation is thought to play a major role in the development of metabolic complications and disease such as insulin resistance and diabetes. We know that different adipose tissue depots contribute differently to the risk of metabolic disease. People who have an upper body fat distribution around the abdomen are at greater risk of disease than those who tend to store fat in their lower body around the hips and thighs. Thus, it is conceivable that adipose tissue depots contribute differently to the inflammatory milieu as a result of varied infiltration of immune cell types. In this review, we describe the role and function of major resident immune cells in the development of adipose tissue inflammation and discuss their regional differences in the context of metabolic disease risk. We find that although initial studies have found regional differences, a more comprehensive understanding of how immune cells interrupt adipose tissue homeostasis is needed.