The Key Role of Akt Protein Kinase in Metabolic-Inflammatory Pathways Cross-Talk: TNF-α Down-Regulation and Improving of Insulin Resistance in HepG2 Cell Line.

BACKGROUND: Elevation of plasma free fatty acids as a principal aspect of type 2 diabetes maintains etiologically insulin insensitivity in target cells. TNF-α inhibitory effects on key insulin signaling pathway elements remain to be verified in insulinresistant hepatic cells. Thus, TNF-α knockdown effects on the key elements of insulin signaling were investigated in the palmitate-induced insulin-resistant hepatocytes. The Akt serine kinase, a key protein of the insulin signaling pathway, phosphorylation was monitored to understand the TNF-α effect on probable enhancing of insulin resistance. METHODS: Insulin-resistant HepG2 cells were produced using 0.5 mM palmitate treatment and shRNA-mediated TNF-α gene knockdown and its down-regulation confirmed using ELISA technique. Western blotting analysis was used to assess the Akt protein phosphorylation status. RESULTS: Palmitate-induced insulin resistance caused TNF-α protein overexpression 1.2-, 2.78, and 2.25- fold as compared to the control cells at post-treatment times of 8 h, 16 h, and 24 h, respectively. In the presence of palmitate, TNF-α expression showed around 30% reduction in TNF-α knockdown cells as compared to normal cells. In the TNF-α down-regulated cell, Akt phosphorylation was approximately 62% more than control cells after treatment with 100 nM insulin in conjugation with 0.5 mM palmitate. CONCLUSIONS: The obtained data demonstrated that TNF-α protein expression reduction improved insulin-stimulated Akt phosphorylation in the HepG2 cells and decreased lipidinduced insulin resistance of the diabetic hepatocytes.

Obesity: A preventable, treatable, but relapsing disease.

In 2013, the American Medical Association recognized obesity as a disease, of growing scientific, social, and political interest. In 2016 in the United States, prevalence rates of preobesity and obesity exceeded 60%. In Italy, these rates exceeded 40%. Total costs related to excess weight reached 9.3% of the U.S. gross domestic product, whereas in Italy the total annual cost of diabetes alone was estimated at 20.3 billion euros/y. The expansion of adipose tissue and visceral fat causes compression, joint stress, metabolic disorders, organ dysfunction, and increased mortality. The increase in peripheral and central fat mass is a chronic and potentially reversible process with appropriate diagnosis and treatment. Conversely, fattening can turn into a chronic relapsing form, complicated by comorbidities and cardiovascular events. The increased risk for mortality and morbidity also can affect metabolically healthy obese individuals, if the condition is underestimated, with disease progression. Due to its inaccuracy, body mass index must be replaced with body composition for the diagnosis of obesity. The chances of obesity reversibility are closely linked to improving the diagnosis and to timely nutritional interventions. Generalization and stigma hinder the treatment of obese individuals. The recognition of obesity as a disease and institutional interest can shift the focus onto obesity and not on the obese, with improvements in adherence to prevention plans. Anthropogenic factors and gut microbiota can influence human behavior and food choice, such as food addiction. Obesity has all the criteria to be recognized as a disease. Proper clinical management will lead to cost and complications savings, such as in diabetes. The aim of this review was to discuss in detail the criteria for defining primary obesity as a disease in a step-by-step manner.

Obesity phenotypes and resorption percentage after breast autologous fat grafting: Rule of low-grade inflammation.

BACKGROUND: One of the main reasons why the breast fat grafting was questioned is that there may be lipofilling resorption. In the literature, the resorption rate reported over the 1(st) year is highly variable (20-90%). OBJECTIVE: The aim of this work was to identify the biochemical and clinical parameters, which increase fat graft maintenance in breast reconstruction. MATERIALS AND METHODS: A sample of 19 patients was treated with fat grafting mixed with platelet-rich plasma. A complete screening of anthropometry, body composition, and blood biochemical parameters was assessed using the standardized equipment. Pre- and post-operative evaluation was performed, which included a complete clinical examination, photographic assessment, nuclear magnetic resonance imaging of the soft tissue, and ultrasound. The follow-up period was 2 years. RESULTS: The authors divided the results into two types of patients: "responder" and "not a responder." In the "responder" group patients with normal weight, gynoid fat distribution, obese, with normal blood biochemical parameters, and atherogenic indices but with high preoperative values of platelet-to-lymphocyte ratio (PLR) (174.49) and neutrophil-lymphocyte ratio (NLR) (2.65) showed a greater increase of fat graft maintenance at 6 and 12 months after the last lipofilling session. In the "not responder group" patients with overweight, android fat distribution, obese, high values of atherogenic indices, but with normal preoperative NLR and PLR ratios showed a lower fat graft maintenance at 6 and 12 months. CONCLUSION: We assume, the problem of fat resorption may be resolved by analysis of body composition and by examine the predictive role of preoperative markers of low-grade inflammation.

Bioelectrical impedance analysis-part II: utilization in clinical practice.

BIA is easy, non-invasive, relatively inexpensive and can be performed in almost any subject because it is portable. Part II of these ESPEN guidelines reports results for fat-free mass (FFM), body fat (BF), body cell mass (BCM), total body water (TBW), extracellular water (ECW) and intracellular water (ICW) from various studies in healthy and ill subjects. The data suggests that BIA works well in healthy subjects and in patients with stable water and electrolytes balance with a validated BIA equation that is appropriate with regard to age, sex and race. Clinical use of BIA in subjects at extremes of BMI ranges or with abnormal hydration cannot be recommended for routine assessment of patients until further validation has proven for BIA algorithm to be accurate in such conditions. Multi-frequency- and segmental-BIA may have advantages over single-frequency BIA in these conditions, but further validation is necessary. Longitudinal follow-up of body composition by BIA is possible in subjects with BMI 16-34 kg/m(2) without abnormal hydration, but must be interpreted with caution. Further validation of BIA is necessary to understand the mechanisms for the changes observed in acute illness, altered fat/lean mass ratios, extreme heights and body shape abnormalities.

Bioelectrical impedance analysis--part I: review of principles and methods.

The use of bioelectrical impedance analysis (BIA) is widespread both in healthy subjects and patients, but suffers from a lack of standardized method and quality control procedures. BIA allows the determination of the fat-free mass (FFM) and total body water (TBW) in subjects without significant fluid and electrolyte abnormalities, when using appropriate population, age or pathology-specific BIA equations and established procedures. Published BIA equations validated against a reference method in a sufficiently large number of subjects are presented and ranked according to the standard error of the estimate. The determination of changes in body cell mass (BCM), extra cellular (ECW) and intra cellular water (ICW) requires further research using a valid model that guarantees that ECW changes do not corrupt the ICW. The use of segmental-BIA, multifrequency BIA, or bioelectrical spectroscopy in altered hydration states also requires further research. ESPEN guidelines for the clinical use of BIA measurements are described in a paper to appear soon in Clinical Nutrition.

Nifedipine-induced changes in body composition in hypertensive patients at term.

BACKGROUND: There are few studies on the effect of nifedipine on fluid homeostasis during pregnancy. OBJECTIVE: To assess the variation of body composition at term in patients with normal pregnancy and patients with gestational hypertension (GH) treated with nifedipine. METHODS: Seventeen healthy patients with singleton pregnancies and 12 non-proteinuric patients with gestational hypertension treated with nifedipine were enrolled consecutively from our University Hospital from January 2000 to January 2001. Two evaluations were performed (anthropometric measurements, bioelectric impedance analysis (BIA) at 5, 50 and 100kHz and hematocrit), the first at 36.4+/-3.2 weeks' gestation, the second at 2.1+/-1.6 days of puerperium. The BIA measurements included: fat mass (FM, kg), fat-free mass (FFM, kg), extra-cellular water (ECW, Lt), intra-cellular water (ICW, Lt), total body water (TBW, Lt). Values were analyzed as mean+/-S.D. and statistical analysis was performed by using the Student's t-test for unpaired data. RESULTS: Birthweights were significantly lower in the gestational hypertensive patients (3472.7+/-266.4g versus 2735.8+/-575.9g, P<0.001). At the first study time, systolic and diastolic blood pressure were significantly higher in the hypertensive patients than in control group, notwithstanding the therapy. Interestingly we found pre-delivery and post-delivery TBW higher in gestational hypertensive patients versus the control patients (44.48+/-9.12Lt versus 36.60+/-5.07Lt, P<0.001 and 40.69+/-4.31Lt versus 37.30+/-4.35Lt, P=0.016, respectively). TBW loss after delivery was greater among hypertensive patients (3.79+/-4.81Lt versus -0.70+/-0.72Lt, P<0.001). CONCLUSIONS: Bioelectrical impedance analysis is a practical tool in the follow-up of anti-hypertensive therapy at term gestation. Moreover, nifedipine increases TBW in gestational hypertensive patients, reverting the pathophisiological pattern, yet described elsewhere.