A Rare Mutation in LMNB2 Associated with Lipodystrophy Drives Premature Cell Senescence

Many proteins are causative for inherited partial lipodystrophies, including lamins, the essential constituents of the nuclear envelope scaffold called the lamina. By performing high throughput sequencing on a panel of genes involved in lipodystrophies, we identified a heterozygous mutation in LMNB2 gene (c.700C > T p.(Arg234Trp)) in a female patient presenting early onset type II diabetes, hypertriglyceridemia, and android fat distribution. This mutation is rare in the general population (frequency 0.013% in GnomAD) and was predicted pathogenic by a set of pathogenicity prediction software. Patient-derived fibroblasts showed nuclear shape abnormalities and premature senescence features, which are two typical cellular phenotypes associated with laminopathies. Moreover, we observed an atypical aggregation of lamin B2 in nucleoplasm, which co-distributes with emerin and lamin A/C, along with an abnormal distribution of lamin A/C at the nuclear envelope. Finally, reducing lamin B2 expression level by siRNA targeted toward LMNB2 transcripts resulted in decreased nuclear anomalies and senescence-associated beta-galactosidase, suggesting a role of the mutated protein in the occurrence of the observed cellular phenotype. Altogether, these results suggest that mutations in lamin B2 could produce premature senescence and partial lipodystrophy features as observed with certain mutants of lamin A/C.

Body Fat Distribution and Associated Risk of Cardiovascular Disease in Adults With Cerebral Palsy

Objective: Fat distribution has increasingly been acknowledged as a more significant health parameter than general obesity, in terms of the risk of cardiovascular disease (CVD). We aimed to investigate the regional fat distribution pattern and general body fat characteristics of adults with cerebral palsy (CP), and we explored the risk of CVD in this population.Methods: People aged ≥20 years who were diagnosed with CP were recruited between February 2014 and November 2014. The subjects underwent a structured interview, laboratory studies, and physical examination. The amount and distribution of fat were determined directly by dual-energy X-ray absorptiometry. Laboratory analysis was performed to measure total cholesterol and triglyceride, high-density lipoprotein (HDL), low-density lipoprotein, and fasting plasma glucose levels. The Framingham risk score (FRS) was used to present the 10-year risk for having CVD, and predictors such as sex, age, total cholesterol, HDL, systolic blood pressure, treatment for hypertension, and smoking status were used to calculate the FRS.Results: Ninety-nine adults (58 men, mean age 41.77 ± 8.95 years) with CP were included. The participants consisted of all five levels of the Gross Motor Function Classification System. The mean body mass index (BMI) was 22.52 ± 4.58 kg/m2. According to BMI criteria, 54.9% were overweight and 27.3% were obese. The fat mass index criteria revealed 10.1% excess fat and 7.6% obesity. In univariable regression analysis, age, the timing of physical function deterioration, and android fat percentage were associated with the FRS (p &lt;0.001, p &lt;0.001, and p = 0.007, respectively). In multiple regression analysis, the FRS was associated with age and android fat percentage, based on the following formula: “FRS=−18.549 + 0.410 ∗ Age + 0.577 ∗ Android percent fat (%) (R2=0.528)′′ (p<0.001).Conclusions: Body fat distribution in the android area is significantly associated with future CVD risk in adults with CP.

Metabolic health, menopause, and physical activity—a 4-year follow-up study

Background In women, metabolic health deteriorates after menopause, and the role of physical activity (PA) in mitigating the change is not completely understood. This study investigates the changes in indicators of metabolic health around menopause and evaluates whether PA modulates these changes. Methods Longitudinal data of 298 women aged 48–55 years at baseline participating in the ERMA and EsmiRs studies was used. Mean follow-up time was 3.8 (SD 0.1) years. Studied indicators of metabolic health were total and android fat mass, waist circumference, waist-to-hip ratio (WHR), systolic (SBP) and diastolic (DBP) blood pressure, blood glucose, triglycerides, serum total cholesterol, and high- (HDL-C) and low-density (LDL-C) lipoprotein cholesterol. PA was assessed by accelerometers and questionnaires. The participants were categorized into three menopausal groups: PRE-PRE (pre- or perimenopausal at both timepoints, n = 56), PRE-POST (pre- or perimenopausal at baseline, postmenopausal at follow-up, n = 149), and POST-POST (postmenopausal at both timepoints, n = 93). Analyses were carried out using linear and Poisson mixed-effect models. Results At baseline, PA associated directly with HDL-C and inversely with LDL-C and all body adiposity variables. An increase was observed in total (B = 1.72, 95% CI [0.16, 3.28]) and android fat mass (0.26, [0.06, 0.46]), SBP (9.37, [3.34, 15.39]), and in all blood-based biomarkers in the PRE-POST group during the follow-up. The increase tended to be smaller in the PRE-PRE and POST-POST groups compared to the PRE-POST group, except for SBP. The change in PA associated inversely with the change in SBP (−2.40, [−4.34, −0.46]) and directly with the change in WHR (0.72, [0.05, 1.38]). Conclusions In middle-aged women, menopause may accelerate the changes in multiple indicators of metabolic health. PA associates with healthier blood lipid profile and body composition in middle-aged women but does not seem to modulate the changes in most of the studied metabolic health indicators during the menopausal transition.

Adults with Crohn’s disease exhibit elevated gynoid fat and reduced android fat irrespective of disease relapse or remission

Crohn’s disease (CD) is a debilitating inflammatory bowel condition of unknown aetiology that is growing in prevalence globally. Large-scale studies have determined associations between female obesity or low body mass index (BMI) with risk of CD at all ages or 8– < 40 years, respectively. For males, low BMI entering adult life is associated with increased incidence of CD or ulcerative colitis up to 40 years later. Body composition analysis has shown that combinations of lean tissue loss and high visceral fat predict poor CD outcomes. Here, we assessed dietary intake, physical activity and whole or regional body composition of patients with CD relapse or remission. This anthropometric approach found people with CD, irrespective of relapse or remission, differed from a large representative healthy population sample in exhibiting elevated gynoid fat and reduced android fat. CD is associated with mesenteric adipose tissue, or “creeping fat”, that envelops affected intestine exclusive of other tissue; that fat is localised to the android region of the body. In this context, CD mesenteric adiposity represents a stark juxtaposition of organ-specific and regional adiposity. Although our study population was relatively small, we suggest tentatively that there is a rationale to refer to Crohn’s disease as a fatty intestine condition, akin to fatty liver conditions. We suggest that our data provide early insight into a subject that potentially warrants further investigation across a larger patient cohort.

Waist-Height Ratio and the Risk of Severe Diabetic Eye Disease in Type 1 Diabetes: A 15-Year Cohort Study

Context Obesity prevalence has increased in type 1 diabetes (T1D). However, the relationship between body composition and severe diabetic eye disease (SDED) is unknown. Objective To investigate the associations between body composition and SDED in adults with T1D. Methods From 5401 adults with T1D in the Finnish Diabetic Nephropathy Study, we assessed 3468, and 437 underwent dual-energy X-ray absorptiometry for body composition analysis. The composite outcome was SDED, defined as proliferative retinopathy, laser treatment, antivascular endothelial growth factor treatment, diabetic maculopathy, vitreous hemorrhage, and vitrectomy. Logistic regression analysis evaluated the associations between body composition and SDED. Multivariable Cox regression analysis assessed the associations between the anthropometric measures and SDED. Subgroup analysis was performed by stages of albuminuria. The relevance ranking of each variable was based on the z statistic. Results During a median follow-up of 14.5 (interquartile range 7.8-17.5) years, 886 SDED events occurred. Visceral/android fat ratio was associated with SDED [odds ratio (OR) 1.40, z = 3.13], as well as the percentages of visceral (OR 1.80, z = 2.45) and android fat (OR 1.28, z = 2.08) but not the total body fat percentage. Waist-height ratio (WHtR) showed the strongest association with the SDED risk [hazard ratio (HR) = 1.28, z = 3.73], followed by the waist (HR 1.01, z = 3.03), body mass index (HR 1.03, z = 2.33), and waist-hip ratio (HR 1.15, z = 2.22). The results were similar in normo- and microalbuminuria but not significant in macroalbuminuria. A WHtR ≥ 0.5 increased the SDED risk by 28% at the normo- and microalbuminuria stages. Conclusions WHtR, a hallmark of central obesity, is associated with SDED in individuals with T1D.

Imaging-Based Body Fat Distribution in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

BackgroundWomen with polycystic ovary syndrome (PCOS) are generally considered to be central obese and at higher risks of metabolic disturbances. Imaging methods are the golden standards for detecting body fat distribution. However, evidence based on magnetic resonance imaging (MRI) and computed tomography (CT) is conflicting. This study systematically reviewed the imaging-based body fat distribution in PCOS patients and quantitatively evaluated the difference in body fat distribution between PCOS and BMI-matched controls.MethodsPUBMED, EMBASE, and Web of Science were searched up to December 2019, and studies quantitatively compared body fat distribution by MRI, CT, ultrasound, or X-ray absorptiometry (DXA) between women with PCOS and their BMI-matched controls were included. Two researchers independently reviewed the articles, extract data and evaluated the study quality based on Newcastle-Ottawa Scale (NOS).Results47 studies were included in systematic review and 39 were eligible for meta-analysis. Compared to BMI-matched controls, higher accumulations of visceral fat (SMD 0.41; 95%CI: 0.23-0.59), abdominal subcutaneous fat (SMD 0.31; 95%CI: 0.20-0.41), total body fat (SMD 0.19; 95% CI: 0.06-0.32), trunk fat (SMD 0.47; 95% CI: 0.17-0.77), and android fat (SMD 0. 36; 95% CI: 0.06-0.66) were identified in PCOS group. However, no significant difference was identified in all the above outcomes in subgroups only including studies using golden standards MRI or CT to evaluate body fat distribution (SMD 0.19; 95%CI: -0.04-0.41 for visceral fat; SMD 0.15; 95%CI: -0.01-0.31 for abdominal subcutaneous fat). Moreover, meta-regression and subgroup analyses showed that young and non-obese patients were more likely to accumulate android fat.ConclusionsPCOS women seem to have abdominal fat accumulation when compared with BMI-matched controls. However, MRI- and CT- assessed fat distribution was similar between PCOS and controls, suggesting central obesity may be independent of PCOS. These findings will help us reappraise the relationship between PCOS and abnormal fat deposition and develop specialized lifestyle interventions for PCOS patients.Systematic Review RegistrationPROSPERO, identifier CRD42018102983.

Abdominal Adiposity in Collegiate Football Linemen: A Study of Race and Position

American football linemen are at an increased risk for developing obesity-related diseases. This study evaluated the impact of race and position on abdominal fat (visceral adipose tissue and android fat percentage) in football linemen. Thirty-four offensive and defensive linemen (%fat: 27.1±7.2%) completed a total body dual-energy X-ray absorptiometry scan to estimate visceral fat and android fat percentage. Participants were stratified by race [Black: n=23; White: n=11] and position (Offense: n=18; Defense: n=16). Two separate two-way ANOVA tests [race × position] were completed. For visceral adipose tissue, there was no interaction (p=0.056), but there was an effect of race (Black: 0.57±0.34 kg; White: 1.51±0.56 kg; p <0.001) and position (Offense: 1.22±0.60 kg; Defense: 0.49±0.34 kg; p<0.001). For android fat percentage, there was no interaction (p=0.855) or race effect (Black: 31.5±11.3%; White: 40.9±8.6%; p=0.123); there was a position effect (Offense: 42.1±5.6%; Defense: 26.0±9.9%; p<0.001). Offensive linemen, regardless of race, had greater visceral adipose tissue and android fat percent compared to defensive linemen. White linemen had greater visceral adipose tissue, regardless of position. These results suggest football linemen, especially offensive linemen with increased abdominal adiposity, may benefit from tracking metabolic health during their collegiate career to mitigate obesity-related disease risk once retired from sport.

Males With Traumatic Lower Limb Loss Differ in Body Fat Distribution Compared to Those Without Limb Loss

ABSTRACT Objectives The primary objective was to examine body fat composition in males with traumatic lower limb loss and a comparison group without limb loss. A secondary objective was to determine if there are differences in body fat composition by traumatic limb loss level. Research Methods and Procedures Cross-sectional analyses of baseline in-person intake data was completed at a large military medical center. Data were collected from 2011 to 2020, and analysis was conducted in 2020. Participants (n = 89) included males who sustained traumatic lower limb loss (n = 50) and an age-matched comparison group without limb loss (n = 39). Mean age of participants was 36.0 ± 13.2 years. Main outcomes measured included age, height, body mass index, weight, body fat mass and percent, android fat mass and percent, gynoid fat mass and percent, and android/gynoid percent fat ratio. Differences between groups were assessed using t-tests or Mann–Whitney U tests. Differences between limb loss levels were assessed using one-way ANOVA or Wilcoxon signed-rank test. Results Body fat percent (P = .001), gynoid fat percent (P = .010), android fat mass (P = .01), and percent (P = .02) were higher in the group with limb loss. There were no differences in body fat composition between limb loss levels (P &gt; .05). Conclusion Males with traumatic lower limb loss had a higher body fat percent compared to those without limb loss. Given higher body fat composition in individuals with limb loss and the relationship between body fat composition and cardiovascular disease risk, including body composition analysis with clinical screening could identify changes and allow for early intervention.

Almond Consumption Decreases Android Fat Mass Percentage in Adults With High Android Subcutaneous Adiposity but Does Not Change HbA1c

Objectives The purpose of this study was to determine if the mixed evidence of almond consumption on HbA1c stems from testing people with different body fat distributions (BFD) associated with different risks of glucose intolerance. Methods A 6-month RCT in 134 adults was conducted. Participants were randomly assigned to the almond or control treatment based on their BFD. Those in the almond group consumed 0.75 oz of almonds with their breakfast and as their afternoon snack (1.5 oz almonds/day) every day, and were instructed not to consume any other nuts. Those in the control treatment continued their habitual breakfast and afternoon snack routines, but were instructed not to consume any nuts. At 0 and 6 months, body composition was measured and blood samples were collected for analyses of HbA1c, glycemia and lipemia. Appetite and dietary intake data were recorded at 0, 2, 4, and 6 months and a blood sample was obtained for compliance testing. Body weight was measured every two weeks. An intention-to-treat linear mixed model analysis was performed with Bonferroni pairwise comparisons on diet quality, energy intake, HbA1c, and body composition change values. Results Incorporating almonds into the diet increased total diet quality by 8.3 ± 2.1% over the intervention (P = 0.001). Participants consuming almonds ingested 195 ± 87 kcals/day more than participants in the control group (P = 0.027), but this did not result in differences in body weight (P &gt; 0.3). The almond, high android subcutaneous adiposity (SAT) group had a greater reduction in android fat mass % (P = 0.038), preserved android lean mass % (P = 0.042), and tended to decrease android VAT mass (P = 0.079) compared to those in the control, high SAT group. There were no differences of HbA1c between groups (P &gt; 0.05). Conclusions Incorporating 1.5-oz of almonds into the diet improves diet quality without promoting positive energy balance and weight gain. Long-term consumption of almonds may also improve android composition in those with high android SAT. However, testing people with different BFD does not account for the mixed evidence on almond consumption and HbA1c. Funding Sources This study was funded by the Almond Board of California.

Changes in Regional Fat Distribution and Anthropometric Measures Across the Menopause Transition

Context The relation between the menopause transition (MT) and changes in regional fat distribution is uncertain. Objective To determine whether the MT is associated with the development of central adiposity. Design Longitudinal analysis from the Study of Women’s Health Across the Nation, spanning 1996-2013 (median follow-up 11.8 years). Setting Community-based. Participants 380 women with regional body composition measures by dual energy X-ray absorptiometry. Mean baseline age was 45.7 years; racial/ethnic composition was 16% Black, 41% Japanese and 43% White. Outcomes Changes in android, gynoid and visceral fat and waist and hip circumferences. Results Android fat increased by 1.21% per year (py) and 5.54% py during premenopause and the MT, respectively (each p&lt;0.05). Visceral and gynoid fat began increasing at the MT, annualized changes were 6.24% and 2.03%, respectively (each p &lt;0.05). Postmenopausal annual trajectories decelerated to 1.47% (visceral), 0.90% (android), and -0.87% (gynoid), (all non-zero, p &lt;0.05). Waist girth grew during premenopause (0.55% py), the MT (0.96% py), and postmenopause (0.55% py) (all non-zero, p&lt;0.05; not statistically different from each other). Hip girth grew during premenopause (0.20% py) and the MT (0.35% py) (each non-zero, p&lt;0.05; not statistically different from each other) and decelerated to zero slope in postmenopause. Results are for the White referent; there were statistically significant differences in some trajectories in Black and Japanese women. Conclusions The MT is associated with the development of central adiposity. Waist or hip circumferences are less sensitive to changes in fat distribution.