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Translational insights into the phenotype of sarcopenic obesity
Full text linkFIRST PART: ANIMAL STUDY: Impact of protein intake and high-fat diet on muscle protein synthesis, ectopic lipid infiltration, energy balance and metabolic flexibility in relation to aging in rats
Background Ectopic lipid deposition impairs muscle anabolic response especially during aging. We hypothesized that the anabolic efficiency of dietary protein in skeletal muscle might be affected within the context of high-fat diet.
Aims The objectives of the study were to investigate muscle protein synthesis, intramuscular lipid deposition, energy balance, and metabolic flexibility in response to two levels of protein intake combined to two levels of fat intake.
Methods Two groups of fifty-eight adult and forty-one old male Wistar rats were randomly divided into four groups: isocaloric standard diet (12% protein, 14% lipid, as STD12); isocaloric standard (high-protein) diet (25% protein, 14% lipid, STD25); hypercaloric high-fat (normal-protein) diet (12% protein, 45% lipid, HFD12); and hypercaloric high-fat (high-protein) diet (25% protein, 45% lipid, HFD25). The nutritional intervention lasted 10 weeks. The fractional synthesis (FSR) and absolute synthesis rates (ASR) of mixed muscle proteins were calculated using isotopically labelled C13-valine incorporation in tibialis anterior (TA). Muscle lipid content was assessed using a chromatography-based method. Protein efficiency ratio (PER) was calculated as PER = {100*[weight gain (g)/protein ingested (g)]}. Respiratory exchanges were assessed by indirect calorimetry, and respiratory quotient (RQ) was calculated. Metabolic flexibility and energy homeostasis were evaluated by the analysis of 24h-RQ using the relative cumulative frequency methodology.
Results Rats in the high-fat diet groups self-limited their food intake, so that energy intake was not different among the groups. Regardless of dietary intervention, TA muscle weight was lower in old groups compared to their adult counterparts (all p values < 0.01). FSR was lower in old rats fed the HFD25 compared to the old STD12 group (diet effect : p=0.02), whereas FSR in old groups was higher than adult groups (age effect, all p values < 0.05). When considering the ASR, no differences emerged between groups except for a tendency towards higher ASR values in the old HFD12 group than the STD25 group (diet effect: p=0.09). Only old rats in the HFD12 group exhibited increased intramuscular triacylglycerols in TA (age effect : p=0.02 ; diet effect : HFD12 vs. STD 12: 2.04±1.74 vs. 0.83±0.49ug/g, p=0.02). PER was lower in the HFD25 group than the HFD12 group, regardless of age (old rats: 25.5 ± 6.2 vs. 57.4 ± 20.1, adult rats: 30.7 ± 15.9 vs. 78.84 ± 20.9, diet effect, p<0.05). In both adult and old rats, PER was higher in the HFD12 groups than the STD12 and STD25 groups (diet effect, p<0.05). Old rats in the HFD25 group exhibited lower RQ values than the HFD12 group, indicating that they relied more markedly on lipids as substrate for oxidation (RQ: 0.83 ± 0.04 vs. 0.87 ± 0.01, diet effect, p<0.05). The comparison between RQ and FQ indicated that, save in the HFD25 groups, RQ was higher than FQ, suggesting energy storage.
Conclusion Aging is characterized by a reduced muscle weight despite an increased FSR, suggesting specific alterations in the nutritional regulation of muscle protein turnover. In isocaloric conditions, higher protein intake modulates muscle lipid infiltration, but does not improve age-related anabolic resistance in old rats fed a high-fat diet.
SECOND PART: CLINICAL STUDY: The decline in muscle strength and muscle quality in relation to metabolic derangements in adult women with obesity
Background & Aims: Sarcopenic obesity is a clinical syndrome described especially in the elderly in which excess fat and reduced muscularity coexist. The metabolic and functional characteristics related to sarcopenic obesity have not been thoroughly investigated in the early stages of the aging process. The aim of the present study was to investigate the phenotype of sarcopenic obesity- lean body mass, muscle strength and muscle quality in women with and without the Metabolic Syndrome (MetS), and its relationship with the features of myosteatosis.
Methods: Study participants were enrolled at the Sapienza University, Rome, Italy. Body composition was assessed by DXA. The Handgrip strength test (HGST) was performed. HGST was normalized to arm lean mass to indicate muscle quality; intermuscular adipose tissue (IMAT) and intramyocellular lipid content (IMCL) were measured by magnetic resonance imaging and spectroscopy, as indicators of myosteatosis. Different indices of sarcopenia were calculated, based on appendicular lean mass (ALM, kg) divided by height squared, or weight, or BMI. The NCEP-ATPIII criteria were used to diagnose the MetS. HOMA-IR was calculated. The physical activity level (PAL) was assessed through the IPAQ questionnaire.
Results: 54 women (age: 48±14 years, BMI: 37.9±5.4 kg/m2 ) were included. 54% had the MetS (metabolically unhealthy). HGST/arm lean mass was lower in metabolically unhealthy women than women without the MetS (6.3±1.8 vs. 7.8±1.6, p=0.03). No differences emerged in terms of absolute ALM (kg) or other indices of sarcopenia (ALM/h2 , ALM/weight, or ALM/BMI) between metabolically healthy vs. unhealthy women (p>0.05). Muscle quality (HGST/arm lean mass) was negatively associated with HOMA-IR (p=0.02), after adjustment for age, body fat, hs-CRP levels, and PAL. IMAT, but not IMCL, was significantly higher in obese women with the MetS compared to women without the MetS (p>0.05). No association emerged between HGST/arm lean mass and IMAT or IMCL when HOMA-IR was included in the models.
Conclusion: Insulin resistance, and not myosteatosis per se, may play a role in the decline of muscle strength, leading to the phenotype of dynapenic obesity. Dynapenia may precede the decline of lean body mass in metabolically unhealthy obese women
[Pediatric non-alcoholic fatty liver disease: recent advances and challenges].
No full textNon-alcoholic fatty liver disease (NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use. The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes. A more advanced form of NAFLD, non-alcoholic steatohepatitis (NASH), includes inflammation and liver cell injury, progressive to cryptogenic cirrhosis. Although prevalence in children is very difficult to establish, NAFLD is probably the most common cause of liver disease in preadolescent and adolescent groups. Over the last two decades the rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide. NAFLD is strongly associated with abdominal obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance. Thus, NAFLD shares many features of the metabolic syndrome, a highly atherogenic condition, and its presence could signify a substantial cardiovascular risk. Accurate diagnosis and staging of NAFLD requires liver biopsy. The development of non-invasive surrogate markers and the advancement in imaging technology will aid in the screening of large populations at risk for NAFLD. While the optimal treatment has yet to be determined, lifestyle modification through diet and exercise should be attempted in children diagnosed with NAFLD. This review outlines current understanding, recent advances and challenges on pediatric NAFLD for both clinicians and researchers. Key words: Fatty liver
Treatment of body composition changes in obese and overweight older adults: insight into the phenotype of sarcopenic obesity
No full textIn recent years, mounting interest has been directed to sarcopenic obesity (SO), given the parallel increase of life expectancy and prevalence of obesity in Western countries. The phenotype of SO is characterized by the coexistence of excess fat mass and decreased muscle mass, leading to the impairment of physical performance. The aim of the present review was to summarize the impact of different treatment strategies contrasting body composition changes in older obese and overweight subjects, providing insight into the SO phenotype. Revision questions were formulated; relevant articles were identified from Pubmed through a systematic search strategy: definition of the search terms (sarcopenic obesity, diet, nutritional supplements, physical activity, exercise, pharmacological treatment); limits: papers published in the last 10 years; humans; age ≥ 60 years old; body mass index >25 kg/m2; language: English. Studies dealing with sarcopenia associated to cancer cachexia or neurological diseases, any malignant disease, inflammatory or autoimmune diseases, corticosteroids for systemic use, bedridden subjects, and syndromic obesity were excluded. 14 articles were identified for inclusion in the present systematic review, and were grouped basing on the type of the main intervention: data assessing body composition changes after combined lifestyle interventions, exercise/physical activity, dietary interventions, and pharmacological treatment. Most of the studies were randomized, controlled. Sample size ranged from 12 to 439 subjects, and study duration varied from 6 weeks to 12 months. Weight loss based on diet combined with exercise seems to be the best strategy to adopt for treatment of phenotypic aspects of SO, improving metabolic consequences related to excess fat, preserving lean mass, and allowing functional recovery. © 2014 Springer Science+Business Media New York
Adaptation of the ORTHO-15 test to Polish women and men
No full textThere is a lack of Polish tools to measure behaviour related to orthorexia nervosa. The purpose of the present study was to validate the Polish version of the ORTHO-15 test. 341 women and 59 men (N = 400) were recruited, whose age ranged from 18 to 35 years. Mean age was 23.09 years (SD = 3.14) in women and 24.02 years (SD = 3.87) in men. The ORTHO-15 test and the EAT-26 test were used in the present study. Factor analysis (exploratory and confirmatory analysis) was used in the present study. Exploratory factor analysis performed on the initial 15 items from a random split half of the study group suggested a nine-item two-factor structure. Confirmatory factor analysis performed on the second randomly selected half of the study group supported this two-factor structure of the ORTHO-15 test. The Polish version of the ORTHO-15 test demonstrated an internal consistency (Cronbach's alpha) equal to 0.644. The Polish version of the ORTHO-15 test is a reliable and valuable instrument to assess obsessive attitudes related to healthy and proper nutrition in Polish female and male population
Food Preferences in the Elderly: Molecular Basis
No full textA close relationship exists between nutritional status and health in the elderly. Changes in body composition (in particular sarcopenia) together with chronic diseases, multiple medications, cognitive impairment, depression, and social isolation can act synergistically with the decline in digestive, olfactory and salivary functions as well as in hormonal profile, affecting the nutritional status. Senile anorexia may predispose elderly subjects to protein energy malnutrition which is associated with functional impairment (due to impaired muscle function and/or decreased bone mass), comorbidity (related to immune dysfunction, anemia, reduced cognitive function, poor wound healing), delayed recovery from acute events, and increased mortality.Physiological modifications (impairment of gastrointestinal function, modified satiating effects of different macronutrients, downregulation of signaling proteins and hormones) may lead to reduced energy and/or nutrient intake. In particular modifications of chemosensory functions (distortion of tasting and olfactory function) may induce important changes in food preferences in the elderly. Moreover, modifications of clinical and nutritional status (impairment of functional status, cognitive decline) together with motivations and perceived barriers may represent an important determinant of food choice
Pediatric nonalcoholic fatty liver disease: A clinical and laboratory challenge
No full textThe true prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) is unknown. Challenges in determining the population prevalence of NAFLD include the type of test (and the reference intervals used to define normal and abnormal), the type of population (general population, hospital series), the demographic characteristics of the population sampled, and the nature of the study design. The natural history of pediatric NAFLD remains uncertain. The issue of when to perform a liver biopsy in children with suspected NAFLD remains controversial. Children with NAFLD but normal alanine aminotransferase are rarely investigated. However, evidence of alterations in glucose metabolism parameters should prompt a better understanding of the natural history of pediatric NAFLD not only in terms of the progression of liver disease but also regarding its potential relationship with other health outcomes such as type 2 diabetes mellitus and cardiovascular disease. This evidence could make liver biopsy mandatory in the majority of cases at risk of progressive and severe hepatic and extrahepatic disease. This conclusion, however, raises the question of the feasibility of liver biopsy assessment in an extremely large at risk population, and of the cost/effectiveness of this policy. There is a considerable, continuous interest in reliable, noninvasive alternatives that will allow the prognosis of pediatric NAFLD to be followed in large community or population-based studies
Therapeutic strategies for sarcopenic obesity: a systematic review
No full textTough plenty of literature investigated therapeutic options for body composition changes targeting elderly people, evidence concerning potential treatments of sarcopenic obesity as a unique condition is scarce. The aim of the present review was to summarize recent evidence regarding treatment of sarcopenic obesity in adult and older individuals
Adipocyte signaling affects thyroid-specific gene expression via down-regulation of TTF-2/FOXE1
No full textObesity affects thyroid gland function. Hypothyroidism, thyroid nodules, goiter, and thyroid cancer are more frequent in patients with higher BMI values. Although these data are supported by many clinical and epidemiological studies, our knowledge is very scarce at the molecular level. In this study, we present the first experimental evidence that adipocyte signaling downregulates the expression of thyroid-specific transcription factor 2 (TTF-2/FoxE1). It plays a crucial role in thyroid development and thyroid homeostasis and it is strictly connected to thyroid cancer as well. We provide in vivo and in vitro evidence that inhibition of TTF-2/FoxE1 gene expression is mediated by adipocyte signaling
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