FARREN.DOC 12/22/2008 10:23:30 AM REMOVING THE WRINKLE IN COSMETICS AND DRUG REGULATION: A NOTICE RATING SYSTEM AND EDUCATION PROPOSAL FOR ANTI-AGING COSMECEUTICALS Victoria Farren Anti-aging skincare products often make unrealistic anti-aging claims that mislead consumers, particularly older consumers. Because of the different premarket testing standards for cosmetics and drugs, companies often classify and market their anti-aging skincare products as cosmetics to the FDA in order to avoid more rigorous standards, yet simultaneously emphasize the drug-like qualities of the products to consumers, suggesting that these products are equivalent to drugs. The FDA allows these products, known as "cosmeceuticals," to be classified as cosmetics despite their drug-like appearances and qualities, such as high-tech anti-aging skincare products that use nanotechnology, stem cell research, or DNA. The weakness of the present classification system in handling cosmeceuticals, which fall into the gray area between clearly defined cosmetics and drugs, creates unknown health risks and confuses and misleads consumers about the actual physiological effects of these products. To resolve these two problems, the Federal Food and Drug Administration need not extensively amend its regulations of the cosmetic and drug categories. Rather, the FDA should instate a notice system paired with consumer education, as well as more carefully regulate product claims.
Resistance training improves cardiovascular risk factors in obese women despite a significative decrease in serum adiponectin levelsnature publishing group
intervention and Prevention
Resistance Training Improves Cardiovascular Risk Factors in Obese Women Despite a Significative Decrease in Serum Adiponectin Levels
Javier Ibáñez1, Mikel Izquierdo1, Cristina Martínez-Labari1, Francisco Ortega2, Ana Grijalba3,
Luis Forga4, Fernando Idoate5, Marisol García-Unciti6, José M. Fernández-Real2
and Esteban M. Gorostiaga1
Increased circulating adiponectin and insulin sensitivity are usually observed after body fat loss induced by a weight‑loss diet. Progressive resistance training (PRT) without a concomitant weight‑loss diet significantly decreases visceral fat, thus improving insulin sensitivity. Therefore, the purpose of this study was to ascertain the effects of combined 16‑week PRT and weight‑loss diet on circulating adiponectin and insulin sensitivity index. Thirty‑four obese (BMI: 30–40 kg/m2) women, aged 40–60 year, were randomized to three groups: a control group (C; n = 9); a diet group (WL; n = 12) with a caloric restriction of 500 kcal/d; and a diet plus resistance training group (WL+RT; n = 13) with the same caloric restriction as group WL and a 16‑week supervised whole body PRT of two sessions/week. Both WL and WL+RT groups showed similar decreases in body mass (−6.3% and −7.7%) and visceral fat (−19.9% and −20.5%). WL resulted in an expected increase in circulating levels of adiponectin (P = 0.07) and insulin sensitivity. However, circulating total adiponectin decreased (P < 0.05) in WL+RT group, whereas an improvement in different cardiovascular risk factors (insulin sensitivity, low‑density lipoprotein cholesterol (LDL‑C), etc.) was observed. In conclusion, in obese women a 16‑week combined PRT and weight‑loss diet is accompanied by significant improvements in different cardiovascular risk factors in spite of a significant decrease of circulating adiponectin.
Obesity (2009) Lifestyle changes such as weight loss and regular physical At present, adiponectin may be the most important and promis- activity are recognized as effective nonpharmacological inter- ing adipocytokine for obtaining a better understanding of the link ventions with beneficial effects on metabolic and cardio vascular between obesity and metabolic and cardiovascular disease (1,2). risk factors (6,10). In this context, different studies have dem- Recent studies have revealed that this adipocytokine exhibits onstrated that, without a concomitant weight-loss diet, pro- antidiabetic (3), anti-inflammatory, and antiatherogenic proper- gressive resistance training (PRT) significantly decreases ties (4). Adiponectin has been shown to be secreted principal y visceral fat in older men (11) and women (12), improving by visceral adipose tissue (VAT), the size of this visceral fat depot insulin sensitivity (11). However, at present both the effect being an important correlate of plasma adiponectin levels (5). of PRT on circulating adiponectin and the physiological role Moreover, it is known that an excess of abdominal adipose tis- of adiponectin on the improvement of metabolic and cardio- sue is a better predictor of the development of insulin resistance, vascular risk factors with either body or fat mass loss are as yet type 2 diabetes and cardiovascular disease than the total amount incompletely understood (1,13).
of adipose tissue (6,7). Circulating levels of adiponectin may be In the present study, we hypothesized that a twice-weekly the link between visceral obesity and certain related metabolic PRT would be particularly useful in the context of a weight- abnormalities which contribute to the development of insulin loss diet in adult obese women, increasing the visceral fat resistance, type 2 diabetes and atherosclerosis (3,8,9).
loss usually observed with a hypocaloric diet in women (14). 1Studies, Research and Sports Medicine Center, Government of Navarra, Pamplona, Spain; 2Department of Diabetes, Endocrinology and Nutrition. Institut d'Investigació Biomédica de Girona (IdIBGi) CIBER Fisiopatología de la Obesidad y Nutrición, Girona, Spain; 3Department of Clinical Biochemistry, Hospital of Navarra, Pamplona, Spain; 4Department of Endocrinology, Hospital of Navarra, Pamplona, Spain; 5Department of Radiology, Clinica San Miguel, Pamplona, Spain; 6Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain. Correspondence: Received 10 February 2009; accepted 13 July 2009; advance online publication 27 August 2009. This could yield highly favorable changes in circulating anthropometric variables
adiponectin and, as a result, to the metabolic and cardio- Height of the barefoot subjects was measured to the nearest 0.1 cm. vascular risk.
Body mass was measured on the same standard medical scale to an accuracy of ±100 g. Waist and hip circumferences were measured with the subject standing erect with arms at the sides and feet together, wear- Methods and Procedures
ing only underwear. The measurer placed an inelastic tape around the subject, without compressing the skin, on a horizontal plane at the level Thirty-four sedentary, nonsmoking, obese (BMI: 30–40 kg/m2) women, of the last false rib and the buttocks, respectively. The measurement was aged 40–60 years, were recruited through an advertisement in a local recorded to the nearest 0.1 cm.
newspaper. Before inclusion in the study, all candidates were thor- oughly screened using an extensive medical history, resting and maxi- mal exercise electrocardiogram and blood pressure measurements. The volumes of visceral and subcutaneous adipose tissue (SAT) Cardiovascular, neuromuscular, arthritic, pulmonary, or other debili- (abdominal and thigh) and muscle volume in the thigh were meas- tating diseases as determined by one or al of the screening tools were ured by magnetic resonance (MR). MR imaging was performed with reasons for exclusion from the study. None of the subjects received any a 1T magnet (Magnetom Impact Expert; Siemens, Erlangen, Germany) medication. Al the subjects were informed in detail about the possible using body coil The subjects were examined in a supine posi- risks and benefits of the project, and they then signed a written consent tion with both arms positioned paral el along the sides of the body. We form before participating in the study. This project was approved by obtained a spoiled T1-weighted gradient-echo sequence with repetition the ethical committee of the regional Health Department. Participants time = 127 ms and echo time = 6 ms. Each half body volume was scanned were randomized to three groups: a control group (C; n = 9); a diet using two stacks, each containing 10 contiguous 10 mm thick slices. group (WL; n = 12) with a caloric restriction of 500 kcal/day; and a diet Each stack was acquired in 20 s and interleaved slice order was used. A plus resistance training group (WL+RT; n = 13) with the same caloric field of view of 500 mm was used and al the stacks were acquired with restriction as group WL and a 16-week supervised whole-body resist- breath- holding. The total investigation time was about 5 min.
ance training program of two sessions/week. Perimenopausal women MR imaging of both thighs was then obtained. T1-weighted sequence were balanced among groups. The subjects were tested on two differ- was used with a repetition time of 645 min and a spin echo time of 20 ent occasions (weeks 0 and 16) using identical protocols. During the min. The field of view was 500 × 500 mm and the matrix was 512 × 192. 16 weeks of the study the subjects maintained their customary recrea- The slices were 10 mm thick, with no gap between the slices. The thighs tional physical activities (e.g., walking). The baseline characteristics of were scanned using two stacks, each containing 15 contiguous 10 mm the subjects are presente thick slices; the scan was performed axial y from the articular boundary table 1 selected anthropometric, muscle strength, and energy intake and expenditure variables, before and after the 16 weeks of
the intervention (week 0 and week 16)
Control group (n = 9) WL group (n = 12) WL+RT group (n = 13) Body weight (kg) Subcutaneous fat (cc) 11,832 ± 3,326*** 11,954 ± 2,446*** Visceral fat (cc) 2,724 ± 1,052*** 2,633 ± 1,000*** Subcutaneous fat (cc) 84,886 ± 23,867 73,085±20,427*** 10,3912 ± 16,407 87,520 ± 13,826*** Energy intake (kcal/d) Carbohydrates (g/d) Habitual energy expenditure (Kcal/d) 1-RM bench-press (kg) 44.4 ±7.7***,† 1-RM half-squat (kg) 291 ± 73.4***,† Values are expressed as means ± s.d.
*P < 0.05, **P < 0.01, ***P < 0.001 between values in weeks 0 and 16. Differences between groups after intervention: †P < 0.001 between C−WL+RT and WL−WL+RT.
intervention and Prevention
measured by Lipoprint System (Quantimetrix, Redondo Beach, CA). This method is based on electrophoresis of lipid stained serum (Sudan black) in a nondenaturing gel gradient of polyacrylamide. The intra- and interassay coefficients of variation was <2%.
energy intake and energy expenditure analysis
At weeks 0 and 16 all subjects were interviewed by an experienced dieti- tian and given instructions on how to complete food records accurately. Three-day dietary food records (including 1 weekend day) were com- pleted, the records being fil ed out on the actual day of consumption of All food records were analyzed by DIETSOURCE (DietSource program; version 1.0; Novartis, Barcelona, Spain).
Similarly, habitual physical activity was evaluated by accelerometry (TriTrac-R3D System, version 2.04; Madison, WI). The TriTrac-R3D was worn on a belt that was firmly attached to the anterior torso of the subject at the level of the waist. TriTrac monitoring was recorded on a minute- by-minute basis over 2 weekdays and 2 weekend days, coinciding with the days of dietary food records.
Figure 1 Magnetic Resonance of an obese woman's trunk (a) before
and (b) after a 16-week combined progressive resistance training and
Each subject in the WL and WL+RT groups received a varied and well- balanced hypocaloric diet (55% of calories as carbohydrates, 15% as of the lowest external femoral condyle. The images were retrieved from proteins, and the rest as fat) of 500 kcal/day, according to the previous the scanner according to a DICOM (Digital Imaging and Communica- analysis of individual daily energy expenditure by accelerometry. This tions in Medicine) protocol. The acquired axial MR images were trans- diet was designed to elicit a 0.5 kg weight loss per week. The control ferred to an external personal computer running Windows XP. The level group was asked to maintain body weight. Throughout the 16-week of each abdominal image was labeled using sagittal scout images, referred intervention period body weight was recorded once every 2 weeks in to the discal level. We used special y designed image analysis software both WL and WL+RT groups. Also, every 2 weeks each subject of the (SliceOmatic 4.3; Tomovision, Montreal, Quebec, Canada) for quantita- intervention groups participated in a series of 1-h seminars in which tive analysis of the images.
the dietitian taught proper food selection and preparation, eating behavior, control of portion sizes, and modification of binge eating and other adverse habits.
Resting blood samples were drawn at weeks 0 and 16. Venous blood samples were obtained at rest between 8:00 and 9:00 am from the strength testing and training protocol
antecubital vein. In premenopausal women, all blood samples were Lower and upper body maximal strength was assessed using 1 rep- obtained during days 5–9 of the follicular phase to check for possible etition concentric maximum (1-RM) action in a half-squat and in a effects of menstrual phases. Blood was drawn after 12 h of fasting and 1 bench-press position, respectively. A detailed description of the 1-RM day of minimal physical activity. The postintervention (week 16) blood testing procedure can be found elsewhere (15). In brief, in the half- draw occurred 72–96 h after the last exercise session. Whole blood squat the subjects began the test by lifting a bar in contact with the was centrifuged at 3,000 rpm for 15 min and the resulting serum was shoulders with weight plates added to both ends of the bar. On com- then removed and stored at −80 °C until subsequent analysis. Basal mand, the subject performed a concentric extension (as fast as pos- glycemia was analyzed using an enzymatic hexokinase method (Roche sible) of the leg muscles starting from a knee angle of 90° to reach the Diagnostics, Mannheim, Germany). Serum insulin levels were meas- full extension of 180°. In the bench-press the bar was positioned 1 cm ured in duplicate by monoclonal immunoradiometric assay (INSI-CTK above the subject's chest and supported by the bottom stops of the Irma; DiaSorin, Madrid, Spain). Intraassay and interassay coefficients measurement device. Maximal strength half-squat was defined as the of variation were <5%. To estimate insulin resistance, the homeo stasis maximum weight that could be lifted through a full range of motion model assessment (HOMA) index was calculated as fasting insulin with proper form. In all tests, strong verbal encouragement was given concentration (μU/ml) × fasting glucose concentration (mmol/l)/22.5. to each subject to motivate them to perform each test action as maxi- Serum levels of estradiol and progesterone were radioimmunologi- mally and as rapidly as possible. Maximal strength variables showed cal y measured using commercial kits (Immunotech SAS, Marseil e, reliability coefficients ranging from 0.80 to 0.99, and the coefficients France) according to the manufacturer's procedures. The intra- and of variation ranged from 2 to 7%. Before testing and training, each interassay accuracies were 6.2–9.5% and 6.6–10.2% of coefficients of subject was familiarized with the testing procedure of voluntary force variation for estradiol and 3.5–5.8% and 5.1–9.0% of coefficients of production in several submaximal and maximal actions.
variation for progesterone. Serum adiponectin and leptin levels were The strength training program used in the present study was similar to measured by commercial y available enzyme-linked immunosorbent that reported previously (15). Briefly, the subjects were asked to report to assay kits (Linco Research, St Charles, MO). The intra- and interassay the training facility twice a week to perform dynamic resistance exercise coefficients of variation were <8 and 7%, respectively. The lowest lev- for 45–60 min per session. A minimum of 2 days elapsed between two els of adiponectin and leptin that can be detected by these assays are consecutive training sessions.
0.78 and 0.50 ng/ ml, respectively. No significant cross-reactivity with Each training session included two exercises for the leg extensor other cytokines or hormone molecules was detected. Serum triglycer- muscles (bilateral leg press and bilateral knee extension exercises), one ides were measured using Infinity Triglycerides Liquid Stable reagent exercise for the arm extensor muscle (the bench-press) and four to (ThermoElectron, Noble Park, Australia). High-density lipoprotein five exercises for the main muscle groups of the body. Only resistance cholesterol (HDL-C) concentration was analyzed by a homogeneous machines (Technogym, Gambettola, Italy) were used throughout the method (ITC Diagnostics, Barcelona, Spain). Total cholesterol (TC) con- training period. Resistance in this study was progressively increased or centration was determined in serum according to the IL test cholesterol decreased every week for the 16-week training period using a repeti- Trinders method 181618–10 (Instrumentations Laboratory, Lexington, tion maximum approach, so that the loads that brought about a given MA). Low-density lipoprotein cholesterol (LDL-C) concentration was relative intensity remained unchanged from week to week.
During the first 8 weeks of the training period the subjects trained with group. In turn, body mass was significantly diminished after loads of 50–70% of the individual 1-RM, and during the last 8 weeks of 16 week of intervention in WL and WL+RT groups, by −6.3 the training period the loads were 70–80% of the maximum. In addition, from week 8 to week 16 the subjects performed a part (20%) of the leg and −7.7%, respectively; whereas abdominal SAT decreased extensor and bench-press sets with loads ranging from 30 to 50% of the by −18.3 and −21.4% (P < 0.001) and thigh subcutaneous fat maximum. In all the individual exercise sessions performed one of the by −16.4% and −18.9% (P < 0.001), respectively. Likewise, vis- researchers was present to direct and assist each subject towards perform- ceral fat mass was reduced in WL and WL+RT groups by −19.9 ing the appropriate work rates and loads. In all subjects average compli- and −20.5% (P < 0.001), respectively. As expected, in the WL ance with the diet classes and exercise sessions was above 95%.
group a significant loss in thigh muscle mass (−5%, P < 0.05) was observed; however, thigh muscle mass was maintained in the Standard statistical methods were used for the calculation of the means, WL+RT group Final y, by week 16 no significant dif- standard deviation and Pearson product-moment correlation coeffi- ferences between WL and WL+RT groups were observed, either cient. One-way ANOVA was used to determine any differences among the three groups' initial measurements. The resistance training and/or in body mass or abdominal fat, thigh fat or thigh muscle mass.
diet related effects were assessed using a two-way ANOVA with repeated measures (groups × time). When a significant F-value was achieved, Basal relationships between adipocytokines levels
Bonferroni post hoc procedures were performed to locate the pairwise and anthropometric and metabolic variables
differences between the means. Selected relative changes were analyzed In the whole group (n = 34), no correlation was observed via one-way ANOVA. Analyses of covariance (ANCOVA) were used to adjust post-interventional values to compare the data between the between baseline adiponectin levels and VAT or any other groups. For this purpose, preinterventional values were used as covari- measured fat compartment. Adiponectin correlated negatively ates so that the effects of the covariance could be observed.
with waist-to-hip ratio (r = −0.359, P < 0.05). In turn, base- Multiple regression models were used to assess the influence of muscle line leptin levels correlated with VAT (r = 0.352, P < 0.05) and mass and adipose tissue compartment changes on HOMA index vari- with basal insulin and HOMA values (r = 0.397, and r = 0.427, ation and TC changes, taking into account potential factors associated with this variable such as age, changes in BMI, energy intake, fat in diet, respectively, P < 0.05). Leptin also presented a marked adiponectin, leptin, LDL-C, and HDL-C. The models were built in a cus- association with BMI (r = 0.753, P < 0.01), waist (r = 0.606, P < tomized way by the stepwise method. Statistical power calculations for 0.01), hip (r = 0.697, P < 0.01), abdominal SAT (r = 0.720, P < this study ranged from 0.75 to 0.80. The P < 0.05 criterion was used for 0.01), and thigh SAT (r = 0.456, P < 0.01).
relationships between percentage variations in adipocytokine
levels and anthropometric and metabolic variables
Baseline characteristics were similar in the three groups In the WL group the difference between baseline and final andAfter 16 weeks, no significant changes were concentration of adiponectin (Δadiponectin) was significantly observed in the different parameters evaluated in the control correlated to the concomitant changes in ΔHDL-C (r = 0.699, table 2 selected metabolic variables, and lipoprotein profiles before and after the 16-week of the intervention (weeks 0 and 16,
Control group (n = 9) WL group (n = 12) WL+RT group (n = 13) Metabolic variablesFasting plasma glucose (mg/dl)Insulin (μU/ml) HOMA index (10−14/ μU/ml)Leptin (ng/ml) Adiponectin (μg/ml) Estradiol (μg/ml) Progesterone (μg/ml) Lipoprotein profilesTriglycerides (mg/dl) Values are expressed as means ± s.d.
HDL, high-density lipoprotein; HOMA, homeostasis model assessment; LDL, low-density lipoprotein; TC, total cholesterol; VLDL, very low-density lipoprotein.
*P < 0.05, **P < 0.01, ***P < 0.001 between values before and after the 16 weeks of intervention.
intervention and Prevention
P < 0.05). In turn, a marked association was observed between the decrease in leptin levels that were mediated by the loss of changes in leptin (Δleptin) and decrease in waist (Δwaist) (r = body fat. It is known that leptin regulates insulin sensitivity and 0.749, P < 0.01), hip (r = 0.734, P < 0.01), thigh subcutane- glucose homeostasis via two different pathways: one through ous fat (r = 0.757, P < 0.01), abdominal subcutaneous fat (r = an adiposity-dependent mechanism, by controlling energy bal- 0.649, P < 0.05), visceral fat (r = 0.663, P < 0.05), and thigh ance and body fat (increased body adiposity leads to insulin muscle (r = 0.592, P < 0.05). In the WL+RT group, by week 16 resistance), and the other through an adiposity-independent a negative relation was only observed between Δadiponectin pathway mediated by the CNS (18,19). Moreover, in our study and concomitant changes in TC (−0.587, P < 0.05). In turn, a the change in total body fat (P < 0.001) was the most significant marked association was observed between changes in leptin factor impacting on the variation in baseline insulin levels (64% and those observed in body mass (r = 0.729, P < 0.01), hip (r = of its variance), even after accounting for the effects of age and 0.731, P < 0.01), thigh subcutaneous fat (r = 0.809, P < 0.01), changes in energy intake, thigh muscle, leptin, fat in diet, VAT abdominal subcutaneous fat (r = 0.589, P < 0.05), thigh muscle and SAT in a multiple linear regression analysis.
mass (r = 0.592, P < 0.05), HOMA value (r = 0.666, P < 0.05), and basal insulin levels (r = 0.612, P < 0.05).
effect of resistance training on tc and ldl-c
The results of the present study demonstrate a favorable
response of plasma TC and LDL-C to resistance training. The main result of this study shows that a whole-body resist- Indeed, after 16 weeks of intervention, while the lipid profile ance training plus a weight-loss diet in middle-aged obese showed no modification in the WL group, the hypercholeste- women were accompanied by significant improvements in dif- rolemic women in the WL+RT group experienced a signifi- ferent cardiovascular risk factors (insulin sensitivity, baseline cant decrease in TC and LDL-C (Table 2). These results are
insulin levels, TC or LDL-C), in spite of a significant decrease in disagreement with most interventional studies, which show in serum adiponectin levels. Indeed, in the WL+RT group a no improvement in lipid profiles after PRT in adult men (20) decrease in circulating total adiponectin was found in 11 of 13 or women (12,21). Indeed, two recent reviews have concluded subjects (P < 0.05), whereas a parallel improvement in differ- that resistance training does not seem to alter blood lipid and ent cardiovascular risk factors (insulin sensitivity, LDL-C, etc.) lipoprotein levels (10,22). For Braith and Stewart (10) a pos- was observed. In turn, in the WL group a similar diet in terms sible explanation for the lack of significant lipoprotein-lipid of caloric content and nutrient composition, and a loss of body changes with PRT may be the fact that TC values for most mass and adipose tissue of similar magnitude were accompa- study groups have been ≤200 mg/dl at study entry. Individuals nied by no changes in serum adiponectin levels or lipid profile, with normal lipid profiles may require greater exercise stimulus although an increase in insulin sensitivity and a decrease in and energy expenditure, coupled with significant reductions in baseline insulin levels were observed.
body weight, to further improve lipid profiles. Surprisingly, no change in lipid profile was found in the WL group even though dissociation between insulin metabolism
no significant differences were observed between the WL and and circulating adiponectin
WL+RT groups either in improvement in insulin sensitivity or Two mechanisms could explain the dissociation of improve- in diet and habitual caloric expenditure, or in body/fat mass ment in insulin metabolism from the circulating adiponectin loss. Whereas no clear dose–response relation between weight observed in the WL+RT group. First, a decreased amount of loss and lipid modulations could be determined, it would circulating adiponectin, in parallel to an insulin- sensitizing appear that trials that experience a weight reduction >5% effect of resistance training associated with increases in adi- of initial body weight seem to observe the most significant ponectin receptor expression should not be discarded. Available changes in TC and LDL-C concentrations (23). However, this evidence suggests that a relationship between aerobic exercise was not the case with our WL group, in which a decrease of and adiponectin-mediated increases in insulin sensitivity is 6% was not translated into an improvement in lipid profile. In more likely to occur at the level of receptor expression in skel- view of these findings, it may be assumed that chronic resist- etal muscle (16). Second, Abbasi et al. (17) reported that it is ance exercise was the main factor responsible for the lipid pro- possible to dissociate improvements in insulin metabolism with file improvement in our WL+RT group. This suggestion is in weight loss from circulating adiponectin, concluding that other agreement with the results of Fahlman et al. (24), who reported factors (e.g., other adipokynes or cytokines produced in adi- that 10 weeks of resistance training at a rate of three sessions/ pose tissue or elsewhere) may play a role in the improvement of week in overweight older women significantly improved the insulin sensitivity. In our study, a marked relation was observed lipid profile without concurrent changes in weight or diet.
in the WL+RT group between changes in leptin (Δleptin) and concomitant changes in circulating insulin levels and HOMA effect of resistance training on hdl-c
value, these correlations being also present in the whole group As to the significant decrease of HDL-C in the WL+RT group, (n = 34) before the start of the study. These results agree with a this finding agrees with most of the results in the literature. previous study by Ryan (6) that reported the effects of 16 weeks Indeed, a review by Durstine et al. (22) concluded that in of a WL+RT program in obese postmenopausal women, con- women, when bodyweight loss is induced by either dietary cluding that the increase in insulin action may be related to intervention, alone or in combination with exercise, a majority of studies indicate that HDL-C will decrease or not change. In conclusion, our results agree with some previous studies At present, we are unable to find any plausible explanation indicating that there are major controversies around the real for this decrease in serum HDL-C. In our study no correla- physiological meaning of increases in circulating adiponectin tion was found between the variation of this lipid variable and that need to be solved. Moreover, future studies are needed to any other physiological or metabolic factors. Different authors determine whether the mechanism of the decreased circulat- have reported that in nondiabetic individuals, and also in type ing adiponectin found in the present study can be explained 2 diabetic patients, circulating adiponectin is positively associ- by a change in the multiisoforms and/or the levels of receptor ated with plasma HDL-C and negatively correlated with LDL-C expression of this hormone.
and triglycerides (25). In this context, a recent study reported that hypoadiponectinemia was independently associated with acknowledgMents
increased postheparin plasma hepatic lipase activity, which in The study was supported by grant no. 04/1594 from the Instituto de Salud turn could result in reductions in HDL-C (26). Of note in our Carlos III, Ministerio de Sanidad y Consumo, Spain.
study was that the difference between baseline and final con- dIsclosure
centration of adiponectin (Δadiponectin) in the WL group sig- The authors declared no conflict of interest.
nificantly correlated to the concomitant changes in ΔHDL-C (r = 0.699, P < 0.05). However, no relation was found between 2009 The Obesity Society serum adiponectin and any lipid profile variable, either in the whole group (n = 34) before the start of the study or after 16 reFerences
1. Ahima RS. Metabolic actions of adipocyte hormones: focus on adiponectin. weeks of intervention in the WL+RT group. Interestingly, the Obesity 2006;14(Suppl 1):S9–S15.
most significant factor impacting on TC in this WL+RT group 2. Pischon T, Rimm EB. Adiponectin: a promising marker for cardiovascular (95% of its variance) was LDL-C, even after accounting for the disease. Clin Chem 2006;52:797–799.
3. Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT. Adiponectin effects of age, BMI, fat in diet, thigh muscle, VAT, SAT, and multimeric complexes and the metabolic syndrome trait cluster. Diabetes adiponectin in a multiple linear regression analysis.
4. Ajuwon KM, Spurlock ME. Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in Increased serum adiponectin levels may not always be
adipocytes. Am J Physiol Regul Integr Comp Physiol 2005;288:R1220–R1225.
beneficial in terms of good health
5. Motoshima H, Wu X, Sinha MK et al. Differential regulation of adiponectin One could speculate about the physiological meaning of a secretion from cultured human omental and subcutaneous adipocytes: effects significant decrease in serum adiponectin in hypercholes- of insulin and rosiglitazone. J Clin Endocrinol Metab 2002;87:5662–5667.
6. Ryan AS. Insulin resistance with aging. Effects of diet and exercise. Sports terolemic obese women submitted to a PRT program plus a weight-loss diet. Although a state of opinion has been created 7. Lapidus L, Bengtsson C, Larsson B et al. Distribution of adipose tissue and assuming that increased adiponectin levels are beneficial in risk of cardiovascular disease and death: a 12-year follow-up of participants in the population study of women in Gothenburg, Sweden. Br Med J terms of good health and low circulating concentrations of this (Clin Res Ed) 1984;289:1257–1261.
hormone have been shown associated to metabolic and cardio- 8. Hotta K, Funahashi T, Arita Y et al. Plasma concentrations of a novel, vascular disease (3,8,9), in recent years different authors have adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595–1599.
emphasized that increased adiponectin levels may not always 9. Vilarrasa N, Vendrell J, Maravall J et al. Distribution and determinants of be beneficial (27,28). Hadjadj et al. (27) reported increased adiponectin, resistin and ghrelin in a randomly selected healthy population. levels of adiponectin associated with diabetes-related microv- Clin Endocrinol (Oxf) 2005;63:329–335.
ascular complications. More recently, Dekker et al. (28) found 10. Braith RW, Stewart KJ. Resistance exercise training: its role in the prevention of cardiovascular disease. Circulation 2006;113:2642–2650.
that, after adjustment for cardiovascular risk factors, high 11. Ibañez J, Izquierdo M, Argüelles I et al. Twice-weekly progressive resistance adipo nectin was significantly associated with increased all- training decreases abdominal fat and improves insulin sensitivity in older cause and cardiovascular mortality.
men with type 2 diabetes. Diabetes Care 2005;28:662–667.
12. Treuth MS, Hunter GR, Kekes-Szabo T et al. Reduction in intra-abdominal The present study has several limitations. First, the lack adipose tissue after strength training in older women. J Appl Physiol of multiisoforms and receptors of adiponectin. In fact, the results found in this study may be explained by a change in 13. Simpson KA, Singh MA. Effects of exercise on adiponectin: a systematic review. Obesity (Silver Spring) 2008;16:241–256.
these multiisoforms and/or the expression of adiponectin 14. Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL. Effects of weight receptors. However, although the mechanism responsible for loss on regional fat distribution and insulin sensitivity in obesity. Diabetes the decreased circulating adiponectin cannot be discerned, to the best of our knowledge this is the first time in which such a 15. Izquierdo M, Häkkinen K, Ibañez J et al. Effects of strength training on muscle power and serum hormones in middle-aged and older men. J Appl physiological adaptation (i.e., decrease in serum adiponectin with a parallel improvement in insulin sensitivity and other 16. Vu V, Riddell MC, Sweeney G. Circulating adiponectin and adiponectin cardiovascular risk factors) has been observed as a result of receptor expression in skeletal muscle: effects of exercise. Diabetes Metab Res Rev 2007;23:600–611.
an ordinary nonpharmacological treatment of obesity. Second, 17. Abbasi F, Chang SA, Chu JW et al. Improvements in insulin resistance with the different ovarian functional status in women. However, weight loss, in contrast to rosiglitazone, are not associated with changes this limitation was avoided measuring basal circulating estra- in plasma adiponectin or adiponectin multimeric complexes. Am J Physiol Regul Integr Comp Physiol 2006;290:R139–R144.
diol levels (Table 2) and balancing menopausal and perimeno-
18. Pittas AG, Joseph NA, Greenberg AS. Adipocytokines and insulin resistance. pausal women between groups.
J Clin Endocrinol Metab 2004;89:447–452.
intervention and Prevention
19. Ahima RS, Qi Y, Singhal NS, Jackson MB, Scherer PE. Brain 24. Fahlman MM, Boardley D, Lambert CP, Flynn MG. Effects of adipocytokine action and metabolic regulation. Diabetes 2006;55 endurance training and resistance training on plasma lipoprotein profiles in elderly women. J Gerontol A Biol Sci Med Sci 2002;57: 20. Kokkinos PF, Hurley BF, Vaccaro P et al. Effects of low- and high-repetition resistive training on lipoprotein-lipid profiles. Med Sci Sports Exerc 25. Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 21. Blumenthal JA, Matthews K, Fredrikson M et al. Effects of exercise training on cardiovascular function and plasma lipid, lipoprotein, and apolipoprotein 26. Schneider JG, von Eynatten M, Schiekofer S, Nawroth PP, Dugi KA. Low concentrations in premenopausal and postmenopausal women. Arterioscler plasma adiponectin levels are associated with increased hepatic lipase activity in vivo. Diabetes Care 2005;28:2181–2186.
22. Durstine JL, Grandjean PW, Davis PG et al. Blood lipid and lipoprotein 27. Hadjadj S, Aubert R, Fumeron F et al. Increased plasma adiponectin adaptations to exercise: a quantitative analysis. Sports Med concentrations are associated with microangiopathy in type 1 diabetic 23. Varady KA, Jones PJ. Combination diet and exercise interventions for 28. Dekker JM, Funahashi T, Nijpels G et al. Prognostic value of adiponectin the treatment of dyslipidemia: an effective preliminary strategy to lower for cardiovascular disease and mortality. J Clin Endocrinol Metab cholesterol levels? J Nutr 2005;135:1829–1835.
Mechanical competence of ovariectomy-induced compromised bone after single or combined treatment with high-frequency loading and bisphosphonates
OPEN Mechanical competence of ovariectomy-induced compromised bone after single or combined Received: 10 February 2015 Accepted: 28 April 2015 treatment with high-frequency Published: 01 June 2015 loading and bisphosphonatesCamargos G. V.1,3, Bhattacharya P.2, van Lenthe G. H.2, Del Bel Cury A. A.3, Naert I.1, Duyck J.1 & Vandamme K.1