Vanessa D. Sherk

The role for adipose tissue in weight regain after weight loss

Weight regain after weight loss is a substantial challenge in obesity therapeutics. Dieting leads to significant adaptations in the homeostatic system that controls body weight, which promotes overeating and the relapse to obesity. In this review, we focus specifically on the adaptations in white adipose tissues that contribute to the biological drive to regain weight after weight loss. Weight loss leads to a reduction in size of adipocytes and this decline in size alters their metabolic and inflammatory characteristics in a manner that facilitates the clearance and storage of ingested energy. We present the hypothesis whereby the long‐term signals reflecting stored energy and short‐term signals reflecting nutrient availability are derived from the cellularity characteristics of adipose tissues. These signals are received and integrated in the hypothalamus and hindbrain and an energy gap between appetite and metabolic requirements emerges and promotes a positive energy imbalance and weight regain. In this paradigm, the cellularity and metabolic characteristics of adipose tissues after energy‐restricted weight loss could explain the persistence of a biological drive to regain weight during both weight maintenance and the dynamic period of weight regain.

Cardiovascular and perceptual responses to blood‐flow‐restricted resistance exercise with differing restrictive cuffs

The purpose of this study was to determine (i) the cardiovascular responses to acute blood‐flow‐restricted (BFR) resistance exercise and (ii) the influence of applied BFR cuff type on the cardiovascular and perceptual responses.

BMD and bone geometry in transtibial and transfemoral amputees.

Prolonged unloading of bone(s) in the residual limb after amputation may cause significant bone loss in the hip and distal bony end of the residual limb. The purpose of this study was to examine the effect of amputation on bone geometry, volumetric BMD (vBMD), and areal BMD (aBMD) by comparing the intact and residual limbs in unilateral transfemoral and transtibial amputees. Amputees (seven above‐knee; seven below‐knee) and two groups of nonamputee control subjects gave informed consent to participate in this study. aBMD of the dual proximal femur, lumbar spine, and total body was assessed using DXA. Bone geometry and vBMD were assessed at the distal ends of the residual limb and intact limb and at a comparable cross‐sectional slice of the intact limb using pQCT (Stratec XCT 3000). There were no significant group differences in age, height, weight, physical activity, time as an amputee, hours wearing a prosthesis per day, or total body and lumbar spine BMD and BMC. There were significant side × group interactions for total hip, femoral neck, and trochanter BMD, with the amputated side having lower BMD, and differences being most severe in above‐knee amputees. Total and cortical vBMD and area were significantly lower at the end of the residual limb compared with the similar slice of the intact limb for both above‐ and below‐knee amputees. In conclusion, amputees exhibited large decrements in BMD, both at the hip and at the end of the residual limb, compared with the intact side. These lower BMD values put amputees, particularly the above‐knee amputees, at increased risk for osteoporosis and fragility fractures in the hip.

The effect of acute blood-flow-restricted resistance exercise on postexercise blood pressure

Introduction:  Blood‐flow‐restricted (BFR) exercise is an emerging type of exercise that may be particularly beneficial to elderly or special populations. These populations may also benefit from reductions in blood pressure (BP). The effect of BFR exercise on postexercise BP has not been examined; this should first be examined in a young, healthy population as a preliminary investigation.

Interlimb Muscle and Fat Comparisons in Persons With Lower-Limb Amputation

OBJECTIVES To investigate differences in muscle and fat tissue between amputated and intact limbs in subjects with transfemoral and transtibial amputations and to determine the effect of amputation level on limb differences. We hypothesized that the amputated limb would have a higher relative amount of fat than the intact limb, and transfemoral amputees would have greater limb differences in muscle size than transtibial amputees. DESIGN Cross-sectional, repeated-measures design. SETTING Laboratory. PARTICIPANTS Subjects included persons with unilateral transfemoral (TF) (n=5) and transtibial (TT) (n=7) amputations and age- and sex-matched nonamputation controls (n=12). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Muscle cross-sectional areas and fat cross-sectional areas of the end of residual limbs were compared with similar cross-sectional sites of the intact limb by using peripheral quantitative computed tomography scans. Thigh and lower-leg fat mass (FM) and bone-free lean body mass were measured by dual-energy x-ray absorptiometry. RESULTS There was a 93% to 117% difference between limbs in muscle cross-sectional areas for TF and TT. TT had a between-limb difference of 39% for fat cross-sectional areas. Thigh bone-free lean body masses and FM were significantly (P<.05) lower for the amputated limb for both TF and TT. Thigh percent fat was significantly (P<.05) higher in the amputated thigh for TF and TT, but limb differences were greater in TF. CONCLUSIONS Muscle atrophy was prevalent in the residual limb with larger relative amounts of fat in the thighs, especially in TF subjects.

Inflammation marker, damage marker and anabolic hormone responses to resistance training with vascular restriction in older males.

The goal of this study was to examine anabolic hormone, muscle damage marker and inflammation marker responses to two types of resistance training protocols in older men. Thirty‐six healthy older males (mean age = 56·6 ± 0·6 years) completed 6 weeks of high‐intensity resistance training (HI‐RT), low‐intensity resistance training with vascular restriction (LI‐BFR) or no exercise control group (CON) three times per week. Three upper body exercises were performed by both exercise groups at the same intensity (at 80% 1‐RM), but lower body exercises were performed by the HI‐RT group at 80% 1‐RM and by the LI‐BFR group at 20% 1‐RM with vascular restriction. Resting serum creatine kinase (CK), interleukin 6 (IL‐6), insulin‐like growth factor‐I (IGF‐I), IGF binding protein 3 (IGFBP‐3) and testosterone (T) were measured before and after training. No significant group differences in resting CK, IL‐6, IGF‐I, IGFBP‐3 and T were detected following training (P>0·05). In addition, there were no significant changes in muscle cross‐sectional area (CSA), but a trend for significant decreases in the percent changes in thigh subcutaneous fat (P = 0·051). Although training‐induced anabolic hormone response did not reach statistical significance, our findings on CK and IL‐6 indicated that the LI‐BFR training protocol was safe and well tolerated for older men to perform to improve muscular strength.

Relationships Between Body Composition, Muscular Strength, and Bone Mineral Density in Estrogen-Deficient Postmenopausal Women

The purpose of this study was to examine relationships between muscular strength, body composition, and bone mineral density (BMD) in untrained postmenopausal women who are not on hormone replacement therapy (HRT). Fifty-five women (age: 63.3+/-0.6yr) completed menstrual history, physical activity, and calcium intake questionnaires. Total and regional body composition and total body, anteroposterior lumbar spine, nondominant forearm, and right proximal femur BMD were measured using dual-energy X-ray absorptiometry (DXA) (GE Lunar Prodigy, Prodigy enCORE software version 10.50.086, Madison, WI). Participants performed strength tests for 3 upper body and 5 lower body resistance exercises. Women with a relative skeletal muscle mass index (RSMI) value less than 5.45 kg/m(2) were defined as a sarcopenia group (SAR). SAR had significantly (p < 0.05) lower total body and forearm BMD compared with those who were not sarcopenic. BMD sites were significantly correlated with upper body strength (UBS) and lower body strength (LBS) (r = 0.28-0.50, p < 0.01), with the strength of relationship being site specific. Strength and fat mass (FM) significantly predicted total body BMD (R(2) = 0.232-0.241, p < 0.05), FM variables predicted spine BMD (R(2) = 0.109-0.140, p < 0.05), and LBS and RSMI predicted hip BMD sites (R(2) = 0.073-0.237, p < 0.05). Body composition variables failed to significantly predict LBS. In conclusion, the contribution of body composition and strength variables to BMD varied by site as FM was more important for total body, forearm and spine BMD, and LBS exerted greater influence on the hip sites.

Bone loss over 1 year of training and competition in female cyclists.

Objective:To observe changes in hip, spine, and tibia bone characteristics in female cyclists over the course of 1 year of training. Design:Prospective observational study. Setting:Laboratory. Participants:Female cyclists (n = 14) aged 26-41 years with at least 1 year of competition history and intent to compete in 10 or more races in the coming year. Assessment of Risk Factors:Women who train and compete in road cycling as their primary sport. Main Outcome Measures:Total body fat-free and fat mass and lumbar spine and proximal femur areal bone mineral density (aBMD) and bone mineral content (BMC) assessments by dual-energy x-ray absorptiometry. Volumetric BMD and BMC of the tibia were measured by peripheral quantitative computed tomography at sites corresponding to 4%, 38%, 66%, and 96% of tibia length. Time points were baseline and after 12 months of training and competition. Results:Weight and body composition did not change significantly over 12 months. Total hip aBMD and BMC decreased by −1.4% ± 1.9% and −2.1% ± 2.3% (P < 0.02) and subtrochanter aBMD and BMC decreased by −2.1% ± 2.0% and −3.3% ± 3.7% (P < 0.01). There was a significant decrease in lumbar spine BMC (−1.1% ± 1.9%; P = 0.03). There were no significant bone changes in the tibia (P > 0.11). Conclusions:Bone loss in female cyclists was site specific and similar in magnitude to losses previously reported in male cyclists. Research is needed to understand the mechanisms for bone loss in cyclists.

Acute bone marker responses to whole-body vibration and resistance exercise in young women.

Whole-body vibration (WBV) augments the musculoskeletal effects of resistance exercise (RE). However, its acute effects on bone turnover markers (BTM) have not been determined. This study examined BTM responses to acute high-intensity RE and high-intensity RE with WBV (WBV+RE) in young women (n=10) taking oral contraceptives in a randomized, crossover repeated measures design. WBV+RE exposed subjects to 5 one-minute bouts of vibration (20 Hz, 3.38 peak-peak displacement, separated by 1 min of rest) before RE. Fasting blood samples were obtained before (Pre), immediately after WBV (PostVib), immediately after RE (IP), and 30-min after RE (P30). Bone alkaline phosphatase did not change at any time point. Tartrate-resistant acid phosphatase 5b significantly increased (p<0.05) from the Pre to PostVib, then decreased from IP to P30 for both conditions. C-terminal telopeptide of type I collagen (CTX) significantly decreased (p<0.05) from Pre to PostVib and from Pre to P30 only for WBV+RE. WBV+RE showed a greater decrease in CTX than RE (-12.6% ± 4.7% vs -1.13% ± 3.5%). In conclusion, WBV was associated with acute decreases in CTX levels not elicited with RE alone in young women.

The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues

Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding. Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129-SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45 min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint tissue was obtained for histology, immunohistochemistry, and protein analysis. Sedentary Het and WT mice were maintained for comparison. Whole tibias were studied for bone morphometry, finite element analysis, and mechanical testing. Forced running improved joint histology in WT mice. However, when ECSOD levels were reduced, this beneficial effect with running was lost. Het ECSOD runner mice had significantly worse histology scores compared with WT runner mice. Runner mice for both strains had increased bone strength in response to the running protocol, while Het mice showed evidence of a less robust bone structure in both runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint damage when joints were stressed by forced running. The bone tissues responded to increased loading with hypertrophy, regardless of mouse strain. We conclude that ECSOD plays an important role in protecting cartilage from damage caused by mechanical loading.