Thyroid autoimmunity is associated with dietary fat consumption.

CONTEXT: Dietary factors are crucial in the onset and development of autoimmune thyroid disease (AITD), but the relationship between specific fatty acids and AITD remains unexplored. METHODS: We analyzed the US National Health and Nutrition Examination Survey (NHANES) 2007-2012 data on 3949 men and 3964 women aged 20 years and over with valid data on TPOAb, TgAb and details of fat intake, using multivariable regression models to examine the relationship of fat intake and specific fatty acid intake with thyroid autoimmunity. RESULTS: Of the 7913 participants, 7.5% had TgAb seropositivity and 11.9% had TPOAb seropositivity. The seropositivity of TgAb and TPOAb was more common in low-fat intake participants. In the overall population and men, fats were associated with thyroid autoimmunity before and after full adjustment for age, ethnicity, body mass index, smoking status and urine iodine concentration (total fat: OR=0.64, 95% CI 0.49 to 0.83; SFA: OR=0.65, 95% CI 0.51 to 0.84; MUFA: OR=0.65, 95% CI 0.50 to 0.85; PUFA: OR=0.76, 95% CI 0.57 to 0.995, after full adjustment in men). Some specific fatty acids followed a similar pattern. The association between fats and TgAb seropositivity was significant in the overall population and men. The association between fats and TPOAb seropositivity was only found in the overall population. CONCLUSION: We found a strong association between fat consumption and thyroid autoimmunity in the overall population and men from the nationally representative population-based survey. Fat and fatty acid consumption may be of benefit to individuals with thyroid autoimmunity.

Reduced insulin clearance in paediatric metabolic (dysfunction)-associated fatty liver disease and its dual role in beta-cell offload and diabetes risk.

AIM: Diminished hepatic insulin clearance (HIC) is observed in obese adults and is presumed to be mediated by fatty liver. However, few reports have examined HIC in Chinese children with metabolic (dysfunction)-associated fatty liver disease (MAFLD). This study aimed to investigate the correlation between HIC, insulin sensitivity and ß-cell function in obese Chinese children with MAFLD. METHODS: In total, 204 obese children (74 MAFLD) aged 4-17 years were enrolled into this study. HIC, insulin sensitivity and ß-cell function were calculated using the oral glucose tolerance test (1.75 g/kg body weight). Correlation analyses between the HIC and clinical variables were performed using Pearson's product-moment correlation coefficients. HIC and glucose homeostasis were assessed in a high-fat diet mouse model, and liver samples were collected for molecular analysis. RESULTS: Obese children with MAFLD exhibited significantly lower HIC (AUCC-peptide/insulin ratio, p = 0.0019), higher insulin resistance (homeostatic model assessment of insulin resistance, p = 0.002), and increased compensatory ß-cell function (homeostatic model assessment-ß, p = 0.046) than obese children without liver involvement. Notably, HIC was negatively correlated with insulin sensitivity (r = -0.5035, p < 0.0001) and ß-cell function (r = -0.4576, p < 0.0001). However, pancreatic ß-cell dysfunction (p = 0.046) was accompanied by future reduced HIC (p = 0.034) in children with MAFLD in prediabetes. In a high-fat diet mouse model, MAFLD mice showed a 50% reduction in insulin-degrading enzyme expression, consistent with the observed decrease in HIC. CONCLUSIONS: A lower HIC may offload pancreatic ß-cells at an early stage. However, obese children with MAFLD are at risk of developing diabetes, and preventive efforts should be prioritized.

Effects and mechanisms of nutritional interventions on extradigestive complications in obese patients.

BACKGROUND: Obesity is associated with an increased risk of multiple extradigestive complications. Thus, understanding the global epidemiology of obesity and its relationship with extradigestive complications, such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease is important. However, nutritional intervention can positively manage issues associated with obesity. Hence, the identification of the current high prevalence of extradigestive complications among patients with obesity and the potential role of nutritional interventions is also essential. AIM: To determine the relationship between obesity and extradigestive complications and emphasize the importance of nutritional interventions in the management of patients with obesity. METHODS: Overall, 110 patients with obesity admitted to our hospital from February 2020 to November 2022 and 100 healthy individuals were included in the present study. Information of the study population, including demographic characteristics, such as age, sex, body mass index, indicators of extradigestive complications, dietary intake, and biomarkers was collected. The study design, participant selection, interventions, and development of the nutritional intervention program were described. The collected data were analyzed to assess the effect of nutritional interventions on extradigestive complications. RESULTS: As a part of nutritional intervention, the dietary structure was modified to decrease the saturated fatty acid and cholesterol intake and increase the dietary fiber and polyunsaturated fatty acid intake to improve the blood lipid levels and cardiovascular health. Mechanistic studies showed that these nutritional interventions positively affected mechanisms that regulate lipid metabolism, improved inflammatory markers in the blood, and improved vascular functions. CONCLUSION: The study discusses the consistency of the present results with previous findings to assess the clinical significance of the present findings. The study provides direction for future research on improving nutritional intervention strategies.

Effects of rice protein, soy isolate protein, and whey concentrate protein on the digestibility and physicochemical properties of extruded rice starch.

Protein, as the second major component in starchy foods, is crucial for its influence on the physicochemical properties and digestibility of starch. However, the effect of different sources of protein on starch digestibility is still unclear. In this paper, the effects of different sources of proteins (rice protein: RP, soybean isolate protein: SPI, and whey concentrate protein: WPC) on structural features, digestibility, and enzyme activity of extruded rice starch were investigated. The addition of all three proteins reduced the starch digestibility of extrudates. Native SPI and WPC suppressed amyloglucosidase activity, and all three proteins exhibited stronger amyloglucosidase inhibition when hydrolyzed. The rheological properties and Fourier transform infrared spectroscopy results revealed the exogenous proteins and starch interacted through non-covalent bonds and improved the ordered structures in the extrudates. The extrusion process also facilitated the formation of a V-type structure. The sum of SDS and RS content of extrudates was negatively correlated with the content of leached amylose and positively correlated with the ratio of 1047/1022 cm-1 . These findings suggest that the inclusion of exogenous proteins during extrusion can affect starch digestibility through mechanisms such as the interaction with starch molecules, as well as the inhibition of amylase activity. PRACTICAL APPLICATION: This result indicated that the addition of protein during extrusion not only increased the nutritional value of the extrudate, but also decreased the starch digestibility. Extrusion technology can efficiently produce extruded products with protein, expanding further applications of protein in food and providing new healthy staple food options for special populations, such as diabetic and overweight people.

Long-acting PEGylated growth hormone in children with idiopathic short stature.

Objective: To evaluate the safety and efficacy of weekly PEGylated-recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS) in China. Design and methods: This was a multicenter, phase II study in which all subjects were randomized 1:1:1 to weekly s.c. injections of PEG-rhGH 0.1 (low-dose (LD) group) or 0.2 mg/kg/week (high-dose (HD) group) or control for 52 weeks. The primary end point was change (Δ) in height s.d. score (HT-SDS) from baseline to week 52. Secondary end points were height velocity (HV), bone maturity, insulin-like growth factor-1 (IGF-1) SDS, and IGF-1/insulin-like growth factor-binding protein-3 (IGFBP-3) molar ratio. Results: A total of 360 children with ISS were recruited in the study (n = 120 in each group). At week 52, ΔHT-SDS was 0.56 ± 0.26, 0.98 ± 0.35, and 0.20 ± 0.26 in the LD, HD, and control groups, respectively (within-group P < 0.0001; intergroup P < 0.0001). Statistically significant values of ΔHV, IGF-1, IGF-1/IGFBP-3 ratio, and IGF-1 SDS at week 52 from baseline were observed in both treatment groups (P < 0.0001). There were clear dose-dependent responses for all auxological variables. PEG-rhGH was well tolerated throughout the treatment period with treatment-emergent adverse events (TEAEs) reported in 86.5%, 84.6%, and 91.3% of children in the HD, LD, and control groups, respectively. The incidence of TEAEs was similar in all treatment groups despite the difference in doses. A total of 27 (8.7%) children experienced drug-related TEAEs. Conclusion: Fifty-two-week treatment with PEG-rhGH 0.1 or 0.2 mg/kg/week achieved significant improvement in HT-SDS and other growth-related variables, including HV, IGF-1 SDS, and IGF-1/IGFBP-3 ratio, in a dose-dependent manner. Both doses were well tolerated with similar safety profiles.

Effects of whey protein on the in vitro digestibility and physicochemical properties of potato starch.

The aim of this study was to examine the effect of whey protein isolate (WPI) on the digestibility and physicochemical properties of potato starch (PS) after heat treatment. WPI reduced the digestibility of PS and increased the order and aggregation structure of gelatinized PS. Examination of the rheological properties of the PS-WPI mixed system before and after adding different chemicals (sodium chloride, urea, and sodium dodecyl sulfate) indicated an involvement of hydrogen bonds and hydrophobic interactions in the PS-WPI gelatinization system. The pasting properties, swelling power, and thermal properties indicated that WPI suppressed the swelling and gelatinization of PS. The addition of WPI reduced the amylose leaching rate from the starch granules, indicating that the presence of exogenous protein could prevent amylose diffusion from the starch granules. Native WPI and its hydrolysate also inhibited amyloglucosidase activity. These findings indicated that the mechanism by which WPI reduces PS digestion involves hydrophobic interactions and hydrogen bonding between WPI and PS, as well as enzyme activity inhibition.

Insight into the effects of adipose tissue inflammation factors on miR-378 expression and the underlying mechanism.

BACKGROUND/AIMS: Obesity and the related metabolic syndrome have emerged as major public health issues in modern society. miRNAs have been shown to play key roles in regulating obesity-related metabolic syndrome, and some miRNAs regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. miR-378 is a candidate target that was shown to be involved in adipose differentiation, mitochondrial metabolism and systemic energy homeostasis. However, little is known about the regulatory mechanisms of miR-378 expression. To better understand the physiological role of miR-378 in obesity and metabolic syndrome, it is crucial that we understand the regulation of miR-378 gene expression in human adipocytes. METHODS: In this study, we investigated the effects of adipokines and inflammatory cytokines on miR-378 expression using Real-time PCR and the potential regulatory mechanisms using luciferase reporter assays and electrophoretic mobility shift assay (EMSA). Results : We found that adipokines and cytokines upregulated miR-378 expression primarily through SREBP and C/EBP binding sites in the miR-378 promoter region. CONCLUSION: Our findings showed that adipokines induced miR-378 expression and revealed the most likely mechanism of adipokine-induced miR-378 dysregulation in human adipocytes. miRNAs have been shown to function in regulating obesity-related metabolic syndrome, and miR-378 may be a novel target for controlling adipose tissue inflammation. This study offers a theoretical basis for understanding systemic adipose tissue inflammation and may provide new strategies for clinical treatment.

TNF-α, IL-6, and leptin increase the expression of miR-378, an adipogenesis-related microRNA in human adipocytes.

Obesity has become a global public health problem associated with complications including type 2 diabetes, cardiovascular disease, and several cancers. Adipocyte differentiation (adipogenesis) plays an important role in obesity and energy homeostasis. Adipose tissue secretes multiple cytokines and adipokines which can cause the complications of obesity, especially insulin resistance. TNF-α, IL-6, leptin, and resistin have been identified as the main regulators of obesity and insulin activity. miR-378 is highly induced during adipogenesis and has been reported to be positively regulated in adipogenesis. In the current study, matured human adipocytes were treated with TNF-α, IL-6, leptin, or resistin on the 15th day after the induction of human pre-adipocyte differentiation. We demonstrated that TNF-α, IL-6, and leptin upregulated miR-378 expression indicating that miR-378 probably is a novel mediator in the development of insulin resistance related to obesity.

MiR-335, an adipogenesis-related microRNA, is involved in adipose tissue inflammation.

During the development of obesity, adipose tissue releases a host of different adipokines and inflammatory cytokines, such as leptin, resistin, tumor necrosis factor α (TNF-α), Interleukin-6 (IL-6), and adiponectin, which mediate insulin resistance. Recently, some microRNAs (miRNAs) regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. Therefore, the relationship between adipokines and miRNA is worth studying. MiR-335 is an adipogenesis-related miRNA and implicated in both fatty acid metabolism and lipogenesis. In this study, we focused on the association of miR-335 and adipokines, and examined the expression trend of miR-335 during human adipocyte differentiation. Our results showed that miR-335 is significantly upregulated with treatment of leptin, resistin, TNF-α, and IL-6 in human mature adipocytes, and its expression elevated in the process of adipocyte differentiation. Interestingly, the transcriptional regulation of miR-335 by these adipokines seems independent of its host gene (mesoderm-specific transcript homolog, MEST). Thus, we cloned and identified potential promoter of miR-335 within the intron of MEST. As a result, a fragment about 600-bp length upstream sequences of miR-335 had apparent transcription activity. These findings indicated a novel role for miR-335 in adipose tissue inflammation, and miR-335 might play an important role in the process of obesity complications via its own transcription mechanism.

Modulation of hsa-miR-26b levels following adipokine stimulation.

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in post-transcriptional regulation of gene expression. Hsa-miR-26b is an intronic miRNA located in the intron of CTDSP1 (carboxy-terminal domain, RNA polymerase II, polypeptide A, small phosphatase 1). In the present study, the expression of hsa-miR-26b was examined during human preadipocyte differentiation. 15 days after induction of differentiation, mature human adipocytes were treated with adipokines. Hsa-miR-26b was differentially expressed during human preadipocyte differentiation. Tumor necrosis factor-α (TNF-α), leptin and resistin, but not interleukin-6, caused downregulation of hsa-miR-26b expression in adipocytes. These results suggest that the expression of hsa-miR-26b is affected by TNF-α, leptin and resistin and that hsa-miR-26b may be an important mediator in regulating the obesity-related insulin sensitivity and inflammatory responses.

Fluoro-ruby retrograde tracing and three- dimensional visualization of the corticospinal tract in the guinea pig.

Fluoro-ruby was injected into the posterior funiculus of the spinal cord in the cervical (C5-T2) and lumbar (L3-6) segments of adult guinea pigs. The spinal cord was cut into serial frozen sections. The Fluoro-ruby labeling was clearly delineated from the surrounding structure. The labeling traversed the cervical, thoracic and lumbar segments, and was located on the ventral portion of the posterior funiculus on the injected side, proximal to the intermediate zone of the dorsal gray matter. The fluorescence area narrowed rostro-caudally. The spinal cord, spinal cord gray matter and corticospinal tract were reconstructed using 3D-DOCTOR 4.0 software, resulting in a robust three-dimensional profile. Using functionality provided by the reconstruction software, free multi-angle observation and sectioning could be conducted on the spinal cord and corticospinal tract. Our experimental findings indicate that the Fluoro-ruby retrograde fluorescent tracing technique can accurately display the anatomical location of corticospinal tract in the guinea pig and that three-dimensional reconstruction software can be used to provide a three-dimensional image of the corticospinal tract.