Amelioration of obesity-induced white adipose tissue inflammation by Bacillus coagulans T4 in a high-fat diet-induced obese murine model.

AIM: Fresh evidence suggests that B. coagulans can be regarded as a promising therapeutic alternative for metabolic disorders. However, the possible effects of this probiotic on obesity-induced adipose tissue inflammation are unknown. METHODS: C57BL/6j male mice were assigned to a normal-chow diet (NCD) or a high-fat diet (HFD) for 10 weeks. After this period, HFD-fed mice were randomly divided into two groups; HFD control group and HFD plus B. coagulans T4 (IBRC-N10791) for another 8 weeks. B. coagulans T4 was administrated daily by oral intragastric gavage (1 × 109 colony-forming units). KEY FINDINGS: Here, we found that B. coagulans successfully mitigated obesity and related metabolic disorder, as indicated by reduced body weight gain, decreased adiposity, and improved glucose tolerance. B. coagulans T4 administration also inhibited HFD-induced macrophage accumulation in white adipose tissue and switched M1 to M2 macrophages. In parallel, B. coagulans T4 treatment attenuated HFD-induced alteration in mRNA expression of pro/anti-inflammatory cytokines and Tlr4 in white adipose tissue. Moreover, B. coagulans T4 supplementation reduced the Firmicutes/Bacteriodetes ratio and increased the number of Lactobacillus and Faecalibacterium compared to the HFD group. Additionally, a significant increase in propionate and acetate levels in the HFD group was seen following B. coagulans T4 administration. SIGNIFICANCE: Taken together, the present study provides evidence that B. coagulans T4 supplementation exerts anti-obesity effects in part through attenuating inflammation in adipose tissue. The present study will have significant implications for obesity management.

High-density lipoprotein cholesterol efflux capacity in patients with obstructive sleep apnea and its relation with disease severity.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to an accelerated risk of cardiovascular disease (CVD). Some key CVD risk factors are present in patients suffering from OSA such as hypertension, inflammation, oxidative stress, and dyslipidemia. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is proposed as a reliable biomarker of HDL function and the present study aimed to quantify this biomarker in patients with OSA. METHODS: ATP binding cassette subfamily A member 1 (ABCA1), non-ABCA1, and total CEC were determined in 69 polysomnographic-confirmed OSA patients and 23 controls. Moreover, paraoxonase (PON) activities, high-sensitivity C-reactive protein (hsCRP), apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I) circulating levels were quantified in the studied population. RESULTS: All CEC measures were reduced in the OSA group compared to the control group. Strikingly, ABCA1 CEC was diminished in severe OSA in comparison with mild OSA. Furthermore, PON activities and apo A-I showed lower levels, while hsCRP and apo B were elevated in OSA patients compared to controls. Moreover, ABCA1 CEC showed an inverse association with hsCRP and a positive association with apo A-I, while non-ABCA1 CEC presented an association with HDL-C. CONCLUSION: These results suggest the presence of an impaired HDL function in OSA. In particular, ABCA1 CEC was associated with disease severity and inflammation which could be a factor increasing the risk of CVD.

Low level of adiponectin predicts the development of Nonalcoholic fatty liver disease: is it irrespective to visceral adiposity index, visceral adipose tissue thickness and other obesity indices?

We aimed to study the correlation of adiponectin level with insulin resistance (IR), carotid intima-media thickness (cIMT), and various obesity indices especially visceral adipose tissue (VAT) thickness, and visceral adiposity index (VAI), in patients with NAFLD (n = 41), T2D (n = 22), NAFLD + T2D (n = 41), and healthy subjects (n = 20). Results showed the median level of adiponectin in patients with NAFLD (2.97 µg/mL) and ones with NAFLD + T2D (3.21 µg/mL) is significantly lower rather than in controls (4.39 µg/mL). Moreover, VAI is the only predictor for adiponectin concentration in the combination of patient groups and also in all participants independent of IR and other obesity indices. Adiponectin level had also a positive correlation with cIMT and IR in NAFLD patients. Interestingly, lower level of adiponectin was associated with the presence of T2D, NAFLD, and NAFLD + T2D independent of IR and obesity indices. Collectively, it seems that VAI reflecting visceral adipose tissue function is a possible predictor of adiponectin level.

Increased circulating level of CTRP15 in patients with type 2 diabetes mellitus and its relation with inflammation and insulin resistance.

AIMS: Type 2 diabetes mellitus (T2DM) is a highly prevalence disease that has a close relation with secretory factors such as adipokines and myokines. C1q tumor necrosis factor-α (TNF-α)-related protein 15 (CTRP15) is a paralogue paralogue of adiponectin that has a close relation with insulin resistance and inflammation. The present study aimed to assess circulating levels of CTRP15 in patients with T2DM in comparison with controls and thier association with inflammatory cytokines. METHODS: This case-control study was performed on 80 T2DM patients and 80 controls which diagnosed according to the criteria of American Diabetes Association (ADA). Serum levels of CTRP15, adiponectin, TNF-α, and interleukin- 6 (IL-6) were determined using ELISA kits. RESULTS: The results indicated higher concentration of CTRP15 in T2DM patients (103.17 ± 27.99) compared to the controls (66.11 ± 20.46, p < 0.001), while adiponectin decreased considerably in the patients compared to the controls (p < 0.001). Moreover, circulating levels of IL-6 and TNF-α elevated in the patients compared to the controls (p < 0.001). CTRP15 indicated independent association with BMI and adiponectin in the controls while, in the patients it demonstrated independent association with HOMA-IR and TNF-α. CONCLUSIONS: Higher concentration of CTRP15 in the patients and its relation with insulin resistance and inflammation suggested a relation of CTRP15 with the pathogenesis of diabetes. In addition, it seems likely that patients with T2DM had a CTRP15 resistance; however, future studies are necessary to prove this concept.

Impaired cholesterol efflux capacity in patients with Helicobacter pylori infection and its relation with inflammation.

BACKGROUND: Gut microorganisms are associated with atherosclerosis and related cardiovascular disease. Helicobacter pylori (H. pylori) infection is associated with dyslipidemia and inflammation contributing to the progression of atherosclerosis. OBJECTIVE: Several studies have reported reduced HDL-C levels in H. pylori infected patients, but HDL cholesterol efflux capacity (CEC) as the most important function of HDL has not been evaluated yet. METHODS: This cross-sectional study was conducted with 44 biopsy confirmed H. pylori patients and 43 controls. ABCA1-mediated, non-ABCA1 and total CEC were measured in ApoB-depleted serum and levels of ApoA-I, ApoB and hsCRP were estimated using ELISA technique. RESULTS: Total and ABCA1 mediated-CEC were reduced in patients compared to controls, independent of age, sex, body mass index and HDL-C (p < 0.001), while non-ABCA1 CEC indicated no significant change between the groups. In addition, patients showed lower serum levels of ApoA-I but increased levels of hsCRP when compared to controls. Total CEC and ABCA1-mediated CEC positively correlated with ApoA-I and HDL-C, furthermore, ABCA1-mediated CEC as well as ApoA-I inversely correlated with hsCRP. CONCLUSION: The results of the present study indicate reduced CECs in H. pylori infected patients, especially ABCA1-mediated CEC which is associated with decreased ApoA-I and increased inflammation.

Adipose tissue gene expression of long non-coding RNAs; MALAT1, TUG1 in obesity: is it associated with metabolic profile and lipid homeostasis-related genes expression?

BACKGROUND: Recent studies point toward the possible regulatory roles of two lncRNAs; metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1) in the pathogenesis of obesity-related disorders and regulation of lipogenesis and adipogenesis. In an attempt to understand the molecules involved in human obesity pathogenesis, we aimed to evaluate the expression of MALAT1 and TUG1 in visceral adipose tissues (VAT) and subcutaneous adipose tissues (SAT) of obese women, as compared to normal-weight women. The mRNA expression of possible target genes including peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator-1 alpha (PGC1α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) which are involved in adipogenesis and lipogenesis were also examined. METHODS: This study was conducted on 20 obese [body mass index (BMI) ≥ 30 kg/m 2] female participants and 19 normal-weight (BMI < 25 kg/m 2) female participants. Real-time PCR was performed to investigate the mRNA expression of the above-mentioned genes in VAT and SAT from all participants. RESULTS: The results showed lower mRNA levels of TUG1 in both the VAT and SAT of obese women, compared to normal-weight women. Furthermore, TUG1 expression in SAT positively correlated with BMI, waist circumference (WC), hip circumference, HOMA-IR, and insulin levels, eGFR value, creatinine levels, and hs-CRP in all participants independent of age and HOMA-IR. However, VAT mRNA expression of TUG1 had a positive correlation with obesity indices and HOMA-IR and insulin levels in the whole population. Moreover, SAT mRNA level of TUG1 was positively correlated with SAT gene expression of PGC1α, SREBP-1c, FAS, and ACC independent of age and HOMA-IR. Although mRNA expression of MALAT1 did not differ between two groups for any tissue, it was positively correlated with SAT mRNA levels of SREBP-1c, PPARγ, and their targets; FAS and ACC, as well as with VAT mRNA levels of PGC1α. CONCLUSIONS: It seems likely that TUG1 with distinct expression pattern in VAT and SAT are involved in the regulation of lipogenic and adipogenic genes and obesity-related parameters. However, more studies are necessary to establish this concept.

Adipose tissue mRNA expression of HDAC1, HDAC3 and HDAC9 in obese women in relation to obesity indices and insulin resistance.

It is well-established that an impaired adipose tissue function and morphology caused by a dysregulated gene expression contribute substantially to obesity. Nowadays, animal model studies and in vitro surveys provide evidence for possible roles of HDACs as emerging epigenetic players in the pathogenesis of obesity. However, the clinical pertinence of HDACs in the field of obesity research in humans is not yet obvious. Here, we investigated mRNA expression of HDAC1, 3 and 9 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of obese female participants (n = 20) and normal-weight women (n = 19). We also evaluated the association of the afore-mentioned HDACs gene expression with obesity indices, insulin resistance parameters, and other obesity-related characteristics. Our data revealed the mRNA level of HDAC1 was significantly decreased in both VAT and SAT of obese women, compared to controls. Moreover, the SAT mRNA expression of HDAC3 and VAT mRNA levels of HDAC9 were significantly lower in obese subjects than those found in controls. We observed that HDAC1 and HDAC3 expression in adipose tissue from the whole population is inversely correlated with obesity indices; BMI, waist, hip and waist-to-height ratio (WHtR). Moreover, we found that HDAC3 expression in adipose tissue had an inverse correlation with HOMA-IR, insulin levels, and serum concentration of hs-CRP. Moreover, VAT HDAC9 mRNA level is inversely correlated with obesity indices; BMI, waist, hip and WHtR and with HOMA-IR, insulin levels, and serum concentration of hs-CRP. Hence, it seems that decreased HDAC1,3 and 9 mRNA expression in adipose tissue might be associated with obesity and related abnormalities. However, more studies are needed to establish this concept.