E L Thomas

Human gene for physical performance

A specific genetic factor that strongly influences human physical performance has not so far been reported, but here we show that a polymorphism in the gene encoding angiotensin-converting enzyme does just that. An ‘insertion’ allele of the gene is associated with elite endurance performance among high-altitude mountaineers. Also, after physical training, repetitive weight-lifting is improved eleven-fold in individuals homozygous for the ‘insertion’ allele compared with those homozygous for the ‘deletion’ allele.

Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study

Background: Hepatic steatosis is associated with obesity and type II diabetes. Proton magnetic resonance spectroscopy (1H MRS) is a non-invasive method for measurement of tissue fat content, including intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL). Patients and methods: We used 1H MRS and whole body magnetic resonance imaging (MRI) to assess the relationship between IHCL accumulation, total body adipose tissue (AT) content/distribution, and IMCL content in 11 subjects with biopsy proven hepatic steatosis and 23 normal volunteers. Results: IHCL signals were detectable in all subjects but were significantly greater in hepatic steatosis (geometric mean (GM) 11.5 (interquartile range (IQR) 7.0–39.0)) than in normal volunteers (GM 2.7 (IQR 0.7–9.3); p = 0.02). In the study group as a whole, IHCL levels were significantly greater in overweight compared with lean subjects (body mass index (BMI) >25 kg/m2 (n = 23): GM 7.7 (IQR 4.0–28.6) v BMI <25 kg/m2 (n = 11): GM 1.3 (IQR 0.3–3.6; p = 0.004)). There was a significant association between IHCL content and indices of overall obesity (expressed as a percentage of body weight) for total body fat (p = 0.001), total subcutaneous AT (p = 0.007), and central obesity (subcutaneous abdominal AT (p = 0.001) and intra-abdominal AT (p = 0.001)), after allowing for sex and age. No correlation between IHCL content and IMCL was observed. A significant correlation was observed between serum alanine aminotransferase and liver fat content (r = 0.57, p = 0.006). Conclusions: Our results suggest that hepatic steatosis appears to be closely related to body adiposity, especially central obesity. MRS may be a useful method for monitoring IHCL in future interventional studies.

Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men

Aims/hypothesis. To compare the relation between intramyocellular lipid content, central obesity and insulin sensitivity in Europeans and South Asians. Methods. Cross-sectional study of 40 South Asian and European non-diabetic men matched for age and body mass index. We measured intramyocellular lipid by proton magnetic resonance spectroscopy of soleus muscle, insulin sensitivity by the short insulin tolerance test, per cent body fat by dual-energy x-ray absorptiometry and visceral fat by single-slice computed tomography of the abdomen. Results. South Asians compared with Europeans had a higher mean per cent body fat (26.8 % vs 22.5 %, p = 0.05) and lower insulin sensitivity (mean ± SEM 2.4 ± 0.2 vs 3.4 %/min ± 0.3, p = 0.013). Mean ( ± SEM) intramyocellular lipid content was higher in South Asians than in Europeans (72.1 ± 7.5 vs 53.6 ± 4.9 mmol/kg dry weight, p = 0.046). In Europeans intramyocellular lipid was correlated with per cent body fat (r = 0.50, p = 0.028), waist:hip ratio (r = 0.74, p < 0.001), visceral fat (r = 0.62, p = 0.004) and insulin sensitivity (r = –0.53, p = 0.016). In South Asians intramyocellular lipid was not significantly related to insulin sensitivity or obesity, and the strongest associations of insulin sensitivity were with fasting plasma triglyceride and waist:hip ratio. Conclusion/interpretation. The association of intramyocellular lipid with insulin sensitivity and obesity in Europeans is consistent with the hypothesis that muscle triglyceride mediates the effect of obesity on insulin sensitivity. The absence of a similar relation of insulin sensitivity to intramyocellular lipid in South Asians suggests that other mechanisms underlie the high insulin resistance observed in this group. [Diabetologia (1999) 42: 932–935]

Resistant starch improves insulin sensitivity in metabolic syndrome

Diabet. Med. 27, 391–397 (2010)

Abnormal body composition and reduced bone mass in growth hormone deficient hypopituitary adults

OBJECTIVES The role of growth hormone in maintaining normal body composition and bone strength In adults has attracted much interest recently. We have assessed body composition and bone mass in GH deficient hypopituitary adults on conventional replacement therapy and compared them with matched controls.

Distribution of adipose tissue in the newborn.

Regional differences in adipose tissue distribution are associated with differences in adipocyte metabolism and obesity-related morbidities. Intrauterine growth restriction appears to place individuals at greater risk of obesity associated morbidities in later life. Despite this, little is known regarding the quantity and distribution of adipose tissue in infants during early development. The aim of this study was to compare total and regional adipose tissue content in appropriate-for-gestational-age (AGA) and growth-restricted (GR) newborn infants born at or near term. Whole body adipose tissue magnetic resonance imaging (MRI) was performed as soon as possible after birth. Total and regional adipose tissue depots were quantified. A total of 35 infants (10 GR; 25 AGA) were studied. Mean (SD) total percentage adipose tissue was lower in GR infants than AGA infants [GR: 17.70% (2.17); AGA: 23.40% (3.85); p = 0.003]. This difference arose from differences in subcutaneous adipose tissue mass [mean (SD) percentage subcutaneous adipose tissue mass, GR: 16.13% (2.20); AGA: 21.44% (3.81); p = 0.004], but not intra-abdominal adipose tissue mass [mean (SD) percentage intra-abdominal adipose tissue, GR: 0.42% (0.22); AGA: 0.61% (0.31); p = 0.45]. In contrast to subcutaneous adipose tissue, intra-abdominal adipose tissue is not reduced in infants with intrauterine growth restriction. This suggests that subcutaneous and intra-abdominal adipose tissue compartments may be under different regulatory control during intrauterine life.

The Influence of Maternal Body Mass Index on Infant Adiposity and Hepatic Lipid Content

Maternal overweight and obesity are associated with adverse offspring outcome in later life. The causal biological effectors are uncertain. Postulating that initiating events may be alterations to infant body composition established in utero, we tested the hypothesis that neonatal adipose tissue (AT) content and distribution and liver lipid are influenced by maternal BMI. We studied 105 healthy mother-neonate pairs. We assessed infant AT compartments by whole body MR imaging and intrahepatocellular lipid content by 1H MR spectroscopy. Maternal BMI ranged from 16.7 to 36.0. With each unit increase in maternal BMI, having adjusted for infant sex and weight, there was an increase in infant total (8 mL; 95% CI, 0.09–14.0; p = 0.03), abdominal (2 mL; 95% CI, 0.7–4.0; p = 0.005), and nonabdominal (5 mL; 95% CI, 0.09–11.0; p = 0.054) AT, and having adjusted for infant sex and postnatal age, an increase of 8.6% (95% CI, 1.1–16.8; p = 0.03) in intrahepatocellular lipid. Infant abdominal AT and liver lipid increase with increasing maternal BMI across the normal range. These effects may be the initiating determinants of a life-long trajectory leading to adverse metabolic health.

Influence of undersampling on magnetic resonance imaging measurements of intra-abdominal adipose tissue

OBJECTIVE: Single-slice magnetic resonance imaging (MRI) and computed tomography (CT) are finding increasing use as methods to estimate visceral fat content in human studies. To assess the validity of this approach, we have compared single- and multi-slice MRI methods for the measurement of intra-abdominal adipose tissue content.MEASUREMENTS: Multi-slice whole-body MR images and single-slices at the level of L2–L3 and L4–L5 were obtained from 59 healthy female volunteers chosen to cover a wide range of body size, and from 17 healthy female volunteers before and after a 6-month exercise intervention.RESULTS: Taking the group as a whole, significant correlation between multi-slice and single-slices was observed (L2–L3: r=0.56; P<0.01; L4–L5: r=0.76; P<0.01). However, the ranking of subjects according to their intra-abdominal fat content was significantly altered by the choice of MRI strategy, especially using L2–L3 methodology. Whole-body (−23.8±20.0%; P<0.01) and single-slice (L2–L3: −31.03±35.0%; P<0.01; L4–L5: −22.1±37.24%; p<0.05) MRI methods also detected a significant decrease in intra-abdominal fat following the exercise protocol, although the latter techniques gave rise to increased spreading of the data from the mean. These results suggest that the use of single-slice imaging techniques can lead to inconsistencies in the estimation of intra-abdominal fat content, which in turn can have significant effects on data interpretation.CONCLUSION: Single-slice MRI appears to be suitable for assessing changes in intra-abdominal fat content in interventional studies, especially in large cohort of subjects, where each subject can serve as its own control. However, for accurate determination of an individuals intra-abdominal fat content, and intersubject comparison, only multi-slice imaging will give precise results.

Whole body fat: Content and distribution

Obesity and its co-morbidities, including type II diabetes, insulin resistance and cardiovascular diseases, have become one of the biggest health issues of present times. The impact of obesity goes well beyond the individual and is so far-reaching that, if it continues unabated, it will cause havoc with the economies of most countries. In order to be able to fully understand the relationship between increased adiposity (obesity) and its co-morbidity, it has been necessary to develop proper methodology to accurately and reproducibly determine both body fat content and distribution, including ectopic fat depots. Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) have recently emerged as the gold-standard for accomplishing this task. Here, we will review the use of different MRI techniques currently being used to determine body fat content and distribution. We also discuss the pros and cons of MRS to determine ectopic fat depots in liver, muscle, pancreas and heart and compare these to emerging MRI techniques currently being put forward to create ectopic fat maps. Finally, we will discuss how MRI/MRS techniques are helping in changing the perception of what is healthy and what is normal and desirable body-fat content and distribution.

Fast and Reproducible Method for the Direct Quantitation of Adipose Tissue in Newborn Infants

The role of body fat content and distribution in infants is becoming an area of increasing interest, especially as perception of its function appears to be rapidly evolving. Although a number of methods are available to estimate body fat content in adults, many are of limited use in infants, especially in the context of regional distribution and internal depots. In this study we developed and implemented a whole-body magnetic resonance imaging (MRI)-based protocol that allows fast and reproducible measurements of adipose tissue content in newborn infants, with an intra-observer variability of<2.4% and an inter-observed variability of<7%. The percentage total body fat for this cohort of infants ranged from 13.3–22.6% (mean and standard deviation: 16.6±2.9%), which agrees closely with published data. Subcutaneous fat accounted for just over 89% of the total body fat, whereas internal fat corresponded to almost 11%, most of which was nonabdominal fat. There were no gender differences in total or regional body fat content. These results show that whole-body MRI can be readily applied to the study of adipose tissue content and distribution in newborn infants. Furthermore, its noninvasive nature makes it an ideal method for longitudinal and interventional studies in newborn infants.