Targeted peripheral focused ultrasound stimulation attenuates obesity-induced metabolic and inflammatory dysfunctions

AbstractObesity, a growing health concern, is associated with an increased risk of morbidity and mortality. Chronic low-grade inflammation is implicated in obesity-driven metabolic complications. Peripheral focused ultrasound stimulation (pFUS) is an emerging non-invasive technology that modulates inflammation. Here, we reasoned that focused ultrasound stimulation of the liver may alleviate obesity-related inflammation and other comorbidities. After 8 weeks on a high-fat high-carbohydrate “Western” diet, C57BL/6J mice were subjected to either sham stimulation or focused ultrasound stimulation at the porta hepatis. Daily liver-focused ultrasound stimulation for 8 weeks significantly decreased body weight, circulating lipids and mitigated dysregulation of adipokines. In addition, liver-focused ultrasound stimulation significantly reduced hepatic cytokine levels and leukocyte infiltration. Our findings demonstrate the efficacy of hepatic focused ultrasound for alleviating obesity and obesity-associated complications in mice. These findings suggest a previously unrecognized potential of hepatic focused ultrasound as a possible novel noninvasive approach in the context of obesity.

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Semi-Quantitative Ultrasonographic Evaluation of NAFLD

Current Pharmaceutical Design ◽

10.2174/1381612826666200417142444 ◽

2020 ◽

Vol 26 (32) ◽

pp. 3915-3927 ◽

Cited By ~ 2

Author(s):

Stefano Ballestri ◽

Claudio Tana ◽

Maria Di Girolamo ◽

Maria Cristina Fontana ◽

Mariano Capitelli ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Imaging Techniques ◽

Metabolic Complications ◽

Nonalcoholic Fatty Liver ◽

Non Invasive ◽

Increased Risk ◽

Risk Of Progression ◽

Progressive Liver Disease

: Nonalcoholic fatty liver disease (NAFLD) embraces histopathological entities ranging from the relatively benign simple steatosis to the progressive form nonalcoholic steatohepatitis (NASH), which is associated with fibrosis and an increased risk of progression to cirrhosis and hepatocellular carcinoma. NAFLD is the most common liver disease and is associated with extrahepatic comorbidities including a major cardiovascular disease burden. : The non-invasive diagnosis of NAFLD and the identification of subjects at risk of progressive liver disease and cardio-metabolic complications are key in implementing personalized treatment schedules and follow-up strategies. : In this review, we highlight the potential role of ultrasound semiquantitative scores for detecting and assessing steatosis severity, progression of NAFLD, and cardio-metabolic risk. : Ultrasonographic scores of fatty liver severity act as sensors of cardio-metabolic health and may assist in selecting patients to submit to second-line non-invasive imaging techniques and/or liver biopsy.

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Maternal Obesity, Inflammation, and Developmental Programming

BioMed Research International ◽

10.1155/2014/418975 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 96

Author(s):

Stephanie A. Segovia ◽

Mark H. Vickers ◽

Clint Gray ◽

Clare M. Reynolds

Keyword(s):

Maternal Obesity ◽

Later Life ◽

Developmental Programming ◽

Health Concern ◽

Low Grade ◽

Critical Periods ◽

Omega 3 ◽

Child Bearing ◽

Prevalence Of Obesity ◽

Low Grade Inflammation

The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming.

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Implication of Auditory Confounding in Interpreting Somatosensory and Motor Responses in Low-Intensity Transcranial Focused Ultrasound Stimulation

Journal of Neurophysiology ◽

10.1152/jn.00701.2020 ◽

2021 ◽

Author(s):

Christine Park ◽

Mengyue Chen ◽

Taewon Kim

Keyword(s):

Focused Ultrasound ◽

Auditory Pathway ◽

Localization Accuracy ◽

Motor Responses ◽

Non Invasive ◽

Low Intensity ◽

Ultrasound Stimulation ◽

Transcranial Focused Ultrasound ◽

Indirect Stimulation ◽

Stimulation Of

Low-intensity transcranial focused ultrasound (LI-tFUS) stimulation is a non-invasive neuromodulation tool that demonstrates high target localization accuracy and depth penetration. It has been shown to modulate activities in the primary motor and somatosensory cortex. Previous studies in animals and humans acknowledged the possibility of indirect stimulation of the peripheral auditory pathway that could confound the somatosensory and motor responses observed with LI-tFUS stimulation. Here, we discuss the implications and interpretations of auditory confounding in the context of neuromodulation.

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PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

BMC Endocrine Disorders ◽

10.1186/s12902-019-0486-9 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Jiayu Huang ◽

Lin Liu ◽

Chunyan Chen ◽

Ying Gao

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary ◽

Predictive Biomarker ◽

Normal Weight ◽

Inflammatory Factors ◽

Low Grade ◽

Model Assessment ◽

Increased Risk ◽

Homeostatic Model Assessment ◽

Low Grade Inflammation

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR. Methods A total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed. Results First, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS. Conclusions Elevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

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Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0523 ◽

2019 ◽

Vol 44 (5) ◽

pp. 512-520 ◽

Cited By ~ 4

Author(s):

Débora Romualdo Lacerda ◽

Michele Macedo Moraes ◽

Albená Nunes-Silva ◽

Kátia Anunciação Costa ◽

Débora Fernandes Rodrigues ◽

...

Keyword(s):

Adipose Tissue ◽

Immune Cells ◽

Aerobic Training ◽

Immune Cell ◽

Control Diet ◽

Moderate Intensity ◽

Low Grade ◽

Carbohydrate Diet ◽

Cytokine Levels ◽

Low Grade Inflammation

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality, and a sedentary lifestyle. The increased consumption of a high-refined carbohydrate (HC) diet is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known nonpharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by an HC diet should be further investigated. Our hypothesis herein was that aerobic training would decrease the recruitment of leukocytes in adipose tissue, thereby reducing the levels of cytokines and improving metabolism in mice fed an HC diet. Male Balb/c mice were assigned to the following groups: control diet/nontrained (C-NT), control diet/trained (C-T), high-refined carbohydrate diet/nontrained (HC-NT), and high-refined carbohydrate diet/trained (HC-T). Mice were submitted to moderate-intensity training sessions that consisted of running 60 min per day for 8 weeks. An intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, relative to HC-NT mice, HC-T mice showed increased resting energy expenditure, decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition. Collectively, our data enhance understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.

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Prepubertal Children Exposed to Maternal Gestational Diabetes Have Latent Low-Grade Inflammation

Hormone Research in Paediatrics ◽

10.1159/000491938 ◽

2018 ◽

Vol 90 (2) ◽

pp. 109-115 ◽

Cited By ~ 1

Author(s):

Leena Antikainen ◽

Jarmo Jääskeläinen ◽

Henrikki Nordman ◽

Raimo Voutilainen ◽

Hanna Huopio

Keyword(s):

Blood Pressure ◽

Lipid Metabolism ◽

Gestational Diabetes ◽

Low Grade ◽

Prepubertal Children ◽

Glucose And Lipid Metabolism ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Hs Crp ◽

Low Grade Inflammation

Background: Maternal gestational diabetes mellitus (GDM) and overweight are associated with an increased risk of obesity and the metabolic syndrome in the adult offspring. We studied the influence of maternal GDM on prepubertal children’s height, weight, body mass index (BMI), lipid and glucose metabolism, and low-grade inflammation. Methods: A cohort of 135 prepubertal Caucasian children (age range 4.4–9.7 years) was studied in a controlled cross-sectional study. Seventy-seven children had been exposed to maternal GDM, and 58 children born after a normal pregnancy served as controls. The outcomes were height, weight, BMI, blood pressure, and biochemical markers of glucose and lipid metabolism and inflammation. Results: There were no differences in height, weight, BMI, fasting serum insulin, plasma glucose, lipids, or blood pressure between the study groups. However, high-sensitivity C-reactive protein (hs-CRP) was significantly higher in the GDM group than in the controls (p = 0.001). Conclusions: Higher hs-CRP as a marker of low-grade inflammation was detected in prepubertal children exposed to maternal GDM, but no differences were seen in height, weight, BMI, or markers of glucose and lipid metabolism compared to control children. This finding may reflect an ongoing process of metabolic changes in children born after a GDM pregnancy.

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Mechanisms Mediating Anti-Inflammatory Effects of Delta-Tocotrienol and Tart Cherry Anthocyanins in 3T3-L1 Adipocytes

Nutrients ◽

10.3390/nu12113356 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3356

Author(s):

Lexie Harlan ◽

London T. Mena ◽

Latha Ramalingam ◽

Shasika Jayarathne ◽

Chwan-Li Shen ◽

...

Keyword(s):

Metabolic Diseases ◽

Combined Treatment ◽

Low Grade ◽

Tart Cherry ◽

Metabolic Complications ◽

Inflammatory Protein ◽

Anti Inflammatory ◽

Low Grade Inflammation ◽

Macrophage Inflammatory Protein

Chronic low-grade inflammation is a primary characteristic of obesity and can lead to other metabolic complications including insulin resistance and type 2 diabetes (T2D). Several anti-inflammatory dietary bioactives decrease inflammation that accompanies metabolic diseases. We are specifically interested in delta-tocotrienol, (DT3) an isomer of vitamin E, and tart cherry anthocyanins (TCA), both of which possess individual anti-inflammatory properties. We have previously demonstrated that DT3 and TCA, individually, reduced systemic and adipose tissue inflammation in rodent models of obesity. However, whether these compounds have combinatorial effects has not been determined yet. Hence, we hypothesize that a combined treatment of DT3 and TCA will have great effects in reducing inflammation in adipocytes, and that these effects are mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), a major inflammatory transcription factor. We used 3T3-L1 adipocytes and treated them with 1–5 µM doses of DT3 along with tart cherry containing 18–36 µg anthocyanin/mL, to assess effects on inflammation. Neither DT3 nor TCA, nor their combinations had toxic effects on adipocytes. Furthermore, pro-inflammatory markers interleukin-6 (IL-6) and p-65 (subunit of NFkB) were reduced at the protein level in media collected from adipocytes with both individual and combined treatments. Additionally, other downstream targets of NFkB including macrophage inflammatory protein 2 (Mip2), and Cyclooxygenase-2 (Cox2) were also significantly downregulated (p ≤ 0.05) when treated with individual and combined doses of DT3 and TCA with no additional combinatorial effects. In summary, DT3 and TCA individually, are beneficial in reducing inflammation with no additional combinatorial effects.

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Host-Modulation Therapy and Chair-Side Diagnostics in the Treatment of Peri-Implantitis

Biosensors ◽

10.3390/bios10050044 ◽

2020 ◽

Vol 10 (5) ◽

pp. 44 ◽

Cited By ~ 3

Author(s):

Timo Sorsa ◽

Joseph Bacigalupo ◽

Mauno Könönen ◽

Pirjo Pärnänen ◽

Ismo T. Räisänen

Keyword(s):

Point Of Care ◽

Low Cost ◽

Diagnostic Tools ◽

Low Grade ◽

Active Matrix ◽

Point Of Care Test ◽

Increased Risk ◽

Prevention And Treatment ◽

Potential Benefits ◽

Low Grade Inflammation

Previous studies report periodontitis and peri-implantitis being able to induce systemic low-grade inflammation, which is known to be associated with increased risk for some systemic medical disease such as cardiovascular disease. In this regard, recent studies have shown that host modulation therapy (HMT) together with traditional mechanical and surgical treatment not only cease the progression of periodontitis but also reduce the systemic collagenolytic biomarkers in both oral fluids and circulation. This suggests that the corresponding adjunctive HMT-medication could be effective in the prevention and treatment of dental peri-implantitis, as well. Furthermore, low-cost, safe, and practical oral fluid active matrix metalloproteinase-8 (aMMP-8) lateral-flow immunotests have been proposed as point-of-care/chair-side diagnostic tools to detect peri-implantitis and periodontitis, and to monitor their effective resolutions, while using various therapeutic strategies, including host modulation. This study reports the potential benefits of HMT-medication in the prevention and treatment of dental peri-implantitis among five patients (four of five were current/ex-smokers). In addition, the aMMP-8 point-of-care test diagnosed 20 peri-implantitis and 20 healthy controls correctly. In conclusion, this study and previous studies support the potential effectiveness of HMT-medication(s) and point-of-care/chair-side technologies in the treatment and diagnostics/monitoring of peri-implantitis. However, more studies are needed to further confirm this.

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High Intake of Sugar and the Balance between Pro- and Anti-Inflammatory Gut Bacteria

Nutrients ◽

10.3390/nu12051348 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1348

Author(s):

Reetta Satokari

Keyword(s):

Saturated Fat ◽

Low Grade ◽

High Intake ◽

Sugar Intake ◽

Metabolic Dysregulation ◽

Gut Barrier Function ◽

Increased Risk ◽

Dietary Sugar ◽

Low Grade Inflammation ◽

Metabolic Endotoxemia

The so-called Western diet is rich in saturated fat and sugars and poor in plant-derived fibers, and it is associated with an increased risk of metabolic and cardiovascular diseases, as well as chronic (low grade) inflammation. The detrimental effects of poor diet are in part mediated by gut microbiota, whose composition, functionality and metabolic end products respond to dietary changes. Recent studies have shown that high intake of sugars increase the relative abundance of Proteobacteria in the gut, while simultaneously decreasing the abundance of Bacteroidetes, which can mitigate the effects of endotoxin, as well as reinforce gut barrier function. Thus, a high sugar intake may stagger the balance of microbiota to have increased pro-inflammatory properties and decreased the capacity to regulate epithelial integrity and mucosal immunity. Consequently, high dietary sugar can, through the modulation of microbiota, promote metabolic endotoxemia, systemic (low grade) inflammation and the development of metabolic dysregulation and thereby, high dietary sugar may have many-fold deleterious health effects, in addition to providing excess energy.

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Mood Disorders, Accelerated Aging, and Inflammation: Is the Link Hidden in Telomeres?

Cells ◽

10.3390/cells8010052 ◽

2019 ◽

Vol 8 (1) ◽

pp. 52 ◽

Cited By ~ 10

Author(s):

Alessio Squassina ◽

Claudia Pisanu ◽

Roberta Vanni

Keyword(s):

Mood Disorders ◽

Accelerated Aging ◽

Cellular Level ◽

Low Grade ◽

Telomere Attrition ◽

Excess Morbidity ◽

Increased Risk ◽

Bidirectional Association ◽

Inflammatory State ◽

Low Grade Inflammation

Mood disorders are associated with an increased risk of aging-related diseases, which greatly contribute to the excess morbidity and mortality observed in affected individuals. Clinical and molecular findings also suggest that mood disorders might be characterized by a permanent state of low-grade inflammation. At the cellular level, aging translates into telomeres shortening. Intriguingly, inflammation and telomere shortening show a bidirectional association: a pro-inflammatory state seems to contribute to aging and telomere dysfunction, and telomere attrition is able to induce low-grade inflammation. Several independent studies have reported shorter telomere length and increased levels of circulating inflammatory cytokines in mood disorders, suggesting a complex interplay between altered inflammatory–immune responses and telomere dynamics in the etiopathogenesis of these disorders. In this review, we critically discuss studies investigating the role of telomere attrition and inflammation in the pathogenesis and course of mood disorders, and in pharmacological treatments with psychotropic medications.

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