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1.
Adipose tissue insulin resistance and lipidome alterations as the characterizing factors of non-alcoholic steatohepatitis.
Guerra, S, Mocciaro, G, Gastaldelli, A
European journal of clinical investigation. 2022;(3):e13695
Abstract
BACKGROUND The prevalence of non-alcoholic fatty liver disease (NAFLD) is now 25% in the general population but increases to more than 55% in subjects with obesity and/or type 2 diabetes. Simple steatosis (NAFL) can develop into more severe forms, that is non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma leading to death. METHODS In this narrative review, we have discussed the current knowledge in the pathophysiology of fatty liver disease, including both metabolic and non-metabolic factors, insulin resistance, mitochondrial function, as well as the markers of liver damage, giving attention to the alterations in lipid metabolism and production of lipotoxic lipids. RESULTS Insulin resistance, particularly in the adipose tissue, is the main driver of NAFLD due to the excess release of fatty acids. Lipidome analyses have shown that several lipids, including DAGs and ceramides, and especially if they contain saturated lipids, act as bioactive compounds, toxic to the cells. Lipids can also affect mitochondrial function. Not only lipids, but also amino acid metabolism is impaired in NAFL/NASH, and some amino acids, as branched-chain and aromatic amino acids, glutamate, serine and glycine, have been linked to impaired metabolism, insulin resistance and severity of NAFLD and serine is a precursor of ceramides. CONCLUSIONS The measurement of lipotoxic species and adipose tissue dysfunction can help to identify individuals at risk of progression to NASH.
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2.
Effect of Standardized Hydrangea serrata (Thunb.) Ser. Leaves Extract on Body Weight and Body Fat Reduction in Overweight or Obese Humans: A Randomized Double-Blind Placebo-Controlled Study.
Han, HS, Chung, KS, Shin, YK, Yu, JS, Kang, SH, Lee, SH, Lee, KT
Nutrients. 2022;(1)
Abstract
Obesity is a major health problem that is caused by body fat accumulation and that can lead to metabolic diseases. Owing to several side effects of the currently used antiobesity drugs, natural plants have risen as safe and potential candidates to alleviate obesity. We have previously reported the antiobesity effect of Hydrangea serrata (Thunb.) Ser. leaves extract (WHS) and its underlying mechanisms. As an extension of our preclinical studies, this study aimed to investigate the effect of WHS on body weight and body fat reduction in overweight or obese humans. A total of 93 healthy overweight or obese males and females, aged 19-65 years, with body mass indexes (BMIs) ≥ 25 and <32 kg/m2, were recruited and received either an oral administration of 600 mg of WHS, or placebo tablets for 12 weeks. Daily supplementation with WHS decreased body weights, body fat masses, and BMIs compared with the placebo-treated group. The hip circumferences, visceral fat areas, abdominal fat areas, and visceral-to-subcutaneous ratios decreased after WHS supplementation. No significant side effects were observed during or after the 12 weeks of WHS intake. In conclusion, WHS, which has beneficial effects on body weight and body fat reduction, could be a promising antiobesity supplement that does not produce any side effects.
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3.
Inter-Day Reliability of Resting Metabolic Rate and Maximal Fat Oxidation during Exercise in Healthy Men Using the Ergostik Gas Analyzer.
Robles-González, L, Gutiérrez-Hellín, J, Aguilar-Navarro, M, Ruiz-Moreno, C, Muñoz, A, Del-Coso, J, R Ruiz, J, Amaro-Gahete, FJ
Nutrients. 2021;(12)
Abstract
The attainment of high inter-day reliability is crucial to determine changes in resting metabolic rate (RMR), respiratory exchange ratio (RER), maximal fat oxidation during exercise (MFO) and the intensity that elicits MFO (Fatmax) after an intervention. This study aimed to analyze the inter-day reliability of RMR, RER, MFO and Fatmax in healthy adults using the Ergostik gas analyzer. Fourteen healthy men (age: 24.4 ± 5.0 years, maximum oxygen uptake (VO2max): 47.5 ± 11.9 mL/kg/min) participated in a repeated-measures study. The study consisted of two identical experimental trials (Day 1 and Day 2) in which the participants underwent an indirect calorimetry assessment at resting and during an incremental exercise test. Stoichiometric equations were used to calculate energy expenditure and substrate oxidation rates. There were no significant differences when comparing RMR (1999.3 ± 273.9 vs. 1955.7 ± 362.6 kcal/day, p = 0.389), RER (0.87 ± 0.05 vs. 0.89 ± 0.05, p = 0.143), MFO (0.32 ± 0.20 vs. 0.31 ± 0.20 g/min, p = 0.776) and Fatmax (45.0 ± 8.6 vs. 46.4 ± 8.4% VO2max, p = 0.435) values in Day 1 vs. Day 2. The inter-day coefficient of variation for RMR, RER, MFO and Fatmax were 4.85 ± 5.48%, 3.22 ± 3.14%, 7.78 ± 5.51%, and 6.51 ± 8.04%, respectively. In summary, the current results show a good inter-day reliability when RMR, RER, MFO and Fatmax are determined in healthy men using the Ergostik gas analyzer.
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4.
Liver fat scores do not reflect interventional changes in liver fat content induced by high-protein diets.
Kabisch, S, Markova, M, Hornemann, S, Sucher, S, Pivovarova-Ramich, O, Machann, J, Hierholzer, J, Rohn, S, Pfeiffer, AFH
Scientific reports. 2021;(1):8843
Abstract
Non-alcoholic fatty liver disease (NAFLD) is common in Metabolic Syndrome and type 2 diabetes (T2DM), driven by energy imbalance, saturated fats and simple carbohydrates. NAFLD requires screening and monitoring for late complications. Liver fat indices may predict NAFLD avoiding expensive or invasive gold-standard methods, but they are poorly validated for use in interventional settings. Recent data indicate a particular insensitivity to weight-independent liver fat reduction. We evaluated 31 T2DM patients, completing a randomized intervention study on isocaloric high-protein diets. We assessed anthropometric measures, intrahepatic lipid (IHL) content and serum liver enzymes, allowing AUROC calculations as well as cross-sectional and longitudinal Spearman correlations between the fatty liver index, the NAFLD-liver fat score, the Hepatosteatosis Index, and IHL. At baseline, all indices predicted NAFLD with moderate accuracy (AUROC 0.731-0.770), supported by correlation analyses. Diet-induced IHL changes weakly correlated with changes of waist circumference, but no other index component or the indices themselves. Liver fat indices may help to easily detect NAFLD, allowing cost-effective allocation of further diagnostics to patients at high risk. IHL reduction by weight-independent diets is not reflected by a proportional change in liver fat scores. Further research on the development of treatment-sensitive indices is required.Trial registration: The trial was registered at clinicaltrials.gov: NCT02402985.
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5.
Effect of exercise on hepatic steatosis: Are benefits seen without dietary intervention? A systematic review and meta-analysis.
Baker, CJ, Martinez-Huenchullan, SF, D'Souza, M, Xu, Y, Li, M, Bi, Y, Johnson, NA, Twigg, SM
Journal of diabetes. 2021;(1):63-77
Abstract
BACKGROUND Interventions involving both exercise and dietary modification are effective in reducing steatosis in nonalcoholic fatty liver disease (NAFLD). However, exercise alone may reduce liver fat and is known to have other positive effects on health. The primary aim of this study was to systematically review the effect of exercise alone without dietary intervention on NAFLD and to examine correlations across changes in liver fat and metabolic markers during exercise. METHODS Relevant online databases were searched from earliest records to May 2020 by two researchers. Studies were included where the trial was a randomized controlled trial, participants were adults, exercise intervention was longer than 4 weeks, no dietary intervention occurred, and the effect of the intervention on liver fat was quantified via magnetic resonance imaging/proton magnetic resonance spectroscopy. RESULTS Of 21 597 studies retrieved, 16 were included involving 706 participants. Exercise was found to have a beneficial effect on liver fat without dietary modification (-2.4%, -3.13 to -1.66) (mean, 95% CI). Pearson correlation showed significant relationships between change in liver fat and change in weight (r = 0.67, P = .007), liver enzymes aspartate aminotransferase (r = 0.76, P = .002) and alanine aminotransferase (r = 0.91, P < .001), and cardiorespiratory fitness VO2 peak (peak volume oxygen consumption) (r = -0.88, P = .004). By multivariate regression, change in weight and change in VO2 peak significantly contributed to change in liver fat (R2 = 0.84, P = .01). CONCLUSIONS This systematic review found that exercise without dietary intervention improves liver fat and that clinical markers may be useful proxies for quantifying liver fat changes.
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6.
Mild intermittent hypoxia exposure induces metabolic and molecular adaptations in men with obesity.
van Meijel, RLJ, Vogel, MAA, Jocken, JWE, Vliex, LMM, Smeets, JSJ, Hoebers, N, Hoeks, J, Essers, Y, Schoffelen, PFM, Sell, H, et al
Molecular metabolism. 2021;:101287
Abstract
OBJECTIVE Recent studies suggest that hypoxia exposure may improve glucose homeostasis, but well-controlled human studies are lacking. We hypothesized that mild intermittent hypoxia (MIH) exposure decreases tissue oxygen partial pressure (pO2) and induces metabolic improvements in people who are overweight/obese. METHODS In a randomized, controlled, single-blind crossover study, 12 men who were overweight/obese were exposed to MIH (15 % O2, 3 × 2 h/day) or normoxia (21 % O2) for 7 consecutive days. Adipose tissue (AT) and skeletal muscle (SM) pO2, fasting/postprandial substrate metabolism, tissue-specific insulin sensitivity, SM oxidative capacity, and AT and SM gene/protein expression were determined. Furthermore, primary human myotubes and adipocytes were exposed to oxygen levels mimicking the hypoxic and normoxic AT and SM microenvironments. RESULTS MIH decreased systemic oxygen saturation (92.0 ± 0.5 % vs 97.1 ± 0.3, p < 0.001, respectively), AT pO2 (21.0 ± 2.3 vs 36.5 ± 1.5 mmHg, p < 0.001, respectively), and SM pO2 (9.5 ± 2.2 vs 15.4 ± 2.4 mmHg, p = 0.002, respectively) compared to normoxia. In addition, MIH increased glycolytic metabolism compared to normoxia, reflected by enhanced fasting and postprandial carbohydrate oxidation (pAUC = 0.002) and elevated plasma lactate concentrations (pAUC = 0.005). Mechanistically, hypoxia exposure increased insulin-independent glucose uptake compared to standard laboratory conditions (~50 %, p < 0.001) and physiological normoxia (~25 %, p = 0.019) through AMP-activated protein kinase in primary human myotubes but not in primary human adipocytes. MIH upregulated inflammatory/metabolic pathways and downregulated extracellular matrix-related pathways in AT but did not alter systemic inflammatory markers and SM oxidative capacity. MIH exposure did not induce significant alterations in AT (p = 0.120), hepatic (p = 0.132) and SM (p = 0.722) insulin sensitivity. CONCLUSIONS Our findings demonstrate for the first time that 7-day MIH reduces AT and SM pO2, evokes a shift toward glycolytic metabolism, and induces adaptations in AT and SM but does not induce alterations in tissue-specific insulin sensitivity in men who are overweight/obese. Future studies are needed to investigate further whether oxygen signaling is a promising target to mitigate metabolic complications in obesity. CLINICAL TRIAL REGISTRATION This study is registered at the Netherlands Trial Register (NL7120/NTR7325).
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7.
Plasticity and heterogeneity of thermogenic adipose tissue.
Sun, W, Modica, S, Dong, H, Wolfrum, C
Nature metabolism. 2021;(6):751-761
Abstract
The perception of adipose tissue, both in the scientific community and in the general population, has changed dramatically in the past 20 years. While adipose tissue was thought for a long time to be a rather simple lipid storage entity, it is now recognized as a highly heterogeneous organ and a critical regulator of systemic metabolism, composed of many different subtypes of cells, with important endocrine functions. Additionally, adipose tissue is nowadays recognized to contribute to energy turnover, due to the presence of specialized thermogenic adipocytes, which can be found in many adipose depots. This review discusses the unprecedented insights that we have gained into the heterogeneity of thermogenic adipocytes and their respective precursors due to the technical developments in single-cell and nucleus technologies. These methodological advances have increased our understanding of how adipose tissue catabolic function is influenced by developmental and intercellular communication events.
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8.
Effect of Dietary Strategies on Respiratory Quotient and Its Association with Clinical Parameters and Organ Fat Loss: A Randomized Controlled Trial.
Goldenshluger, A, Constantini, K, Goldstein, N, Shelef, I, Schwarzfuchs, D, Zelicha, H, Yaskolka Meir, A, Tsaban, G, Chassidim, Y, Gepner, Y
Nutrients. 2021;(7)
Abstract
The relation between changes in respiratory quotient (RQ) following dietary interventions and clinical parameters and body fat pools remains unknown. In this randomized controlled trial, participants with moderate abdominal obesity or/and dyslipidemia (n = 159) were randomly assigned to a Mediterranean/low carbohydrate (MED/LC, n = 80) or a low fat (LF, n = 79) isocaloric weight loss diet and completed a metabolic assessment. Changes in RQ (measured by indirect calorimeter), adipose-tissue pools (MRI), and clinical measurements were assessed at baseline and after 6 months of intervention. An elevated RQ at baseline was significantly associated with increased visceral adipose tissue, hepatic fat, higher levels of insulin and homeostatic insulin resistance. After 6 months, body weight had decreased similarly between the diet groups (-6 ± 6 kg). However, the MED/LC diet, which greatly improved metabolic health, decreased RQ significantly more than the LF diet (-0.022 ± 0.007 vs. -0.002 ± 0.008, p = 0.005). Total cholesterol and diastolic blood pressure were independently associated with RQ changes (p = 0.045). RQ was positively associated with increased superficial subcutaneous-adipose-tissue but decreased renal sinus, pancreatic, and intramuscular fats after adjusting for confounders. Fasting RQ may reflect differences in metabolic characteristics between subjects affecting their potential individual response to the diet.
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9.
Human Milk Drives the Intimate Interplay Between Gut Immunity and Adipose Tissue for Healthy Growth.
van den Elsen, LWJ, Verhasselt, V
Frontiers in immunology. 2021;:645415
Abstract
As the physiological food for the developing child, human milk is expected to be the diet that is best adapted for infant growth needs. There is also accumulating evidence that breastfeeding influences long-term metabolic outcomes. This review covers the potential mechanisms by which human milk could regulate healthy growth. We focus on how human milk may act on adipose tissue development and its metabolic homeostasis. We also explore how specific human milk components may influence the interplay between the gut microbiota, gut mucosa immunity and adipose tissue. A deeper understanding of these interactions may lead to new preventative and therapeutic strategies for both undernutrition and other metabolic diseases and deserves further exploration.
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10.
The Role of Exercise, Diet, and Cytokines in Preventing Obesity and Improving Adipose Tissue.
Atakan, MM, Koşar, ŞN, Güzel, Y, Tin, HT, Yan, X
Nutrients. 2021;(5)
Abstract
The prevalence of obesity continues to rise worldwide despite evidence-based public health recommendations. The promise to adopt a healthy lifestyle is increasingly important for tackling this global epidemic. Calorie restriction or regular exercise or a combination of the two is accepted as an effective strategy in preventing or treating obesity. Furthermore, the benefits conferred by regular exercise to overcome obesity are attributed not only to reduced adiposity or reduced levels of circulating lipids but also to the proteins, peptides, enzymes, and metabolites that are released from contracting skeletal muscle or other organs. The secretion of these molecules called cytokines in response to exercise induces browning of white adipose tissue by increasing the expression of brown adipocyte-specific genes within the white adipose tissue, suggesting that exercise-induced cytokines may play a significant role in preventing obesity. In this review, we present research-based evidence supporting the effects of exercise and various diet interventions on preventing obesity and adipose tissue health. We also discuss the interplay between adipose tissue and the cytokines secreted from skeletal muscle and other organs that are known to affect adipose tissue and metabolism.