ABSTRACT
Obesity has been associated with increased intraocular pressure (IOP), but the results are inconsistent. Recently, a subgroup of obese individuals with good metabolic profiles were suggested to have better clinical outcomes than normal-weight individuals with metabolic diseases. The relationships between IOP and different combinations of obesity and metabolic health status have not been investigated. Therefore, we investigated the IOP among groups with different combinations of obesity status and metabolic health status. We examined 20,385 adults aged 19 to 85 years at the Health Promotion Center of Seoul St. Mary's Hospital between May 2015 and April 2016. Individuals were categorized into four groups according to obesity (body mass index (BMI) ≥ 25 kg/m2) and metabolic health status (defined based on prior medical history or abdominal obesity, dyslipidemia, low high-density lipoprotein cholesterol, high blood pressure, or high fasting blood glucose levels upon medical examination). ANOVA and ANCOVA were performed to compare the IOP among the subgroups. The IOP of the metabolically unhealthy obese group (14.38 ± 0.06 mmHg) was the highest, followed by that of the metabolically unhealthy normal-weight group (MUNW, 14.22 ± 0.08 mmHg), then, the metabolically healthy groups (p < 0.001; 13.50 ± 0.05 mmHg and 13.06 ± 0.03 mmHg in the metabolically healthy obese (MHO) and metabolically healthy normal-weight groups, respectively). Subjects who were metabolically unhealthy showed higher IOP compared to their counterparts who were metabolically healthy at all BMI levels, and there was a linear increase in IOP as the number of metabolic disease components increased, but no difference between normal-weight vs. obese individuals. While obesity, metabolic health status, and each component of metabolic disease were associated with higher IOP, those who were MUNW showed higher IOP than those who were MHO, which indicates that metabolic status has a greater impact than obesity on IOP.
ABSTRACT
The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM19 OVN. GRIM-19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.
ABSTRACT
The functions of adipose tissue are associated with autoimmune diseases, such as rheumatoid arthritis (RA). Some studies have shown that the three compositions of adipose tissue (white, brown, and beige) have different functions. Brown adipose tissue (BAT) is known to secrete several factors that differ from those in white adipose tissue. This suggests that BAT might have potential positive advantages in the physiology of autoimmune diseases. We compared the functions of collagen-induced arthritis mice-derived BAT (CIA BAT) with normal mice-derived BAT. DBA/1J mice (6-7 weeks of age) were immunized by intradermal injection at the base of the tail with 100 µg of bovine type II collagen (CII) emulsified in complete Freund's adjuvant. Immunized mice then received booster immunizations by intraperitoneal injection with 100 µg of CII in incomplete Freund's adjuvant. We transplanted CIA BAT and normal BAT into CIA recipient mice. After transplantation, we measured the functions of CIA BAT and normal BAT in mice. Normal BAT-transplanted mice showed significantly lower scores of bone damage, inflammation, and cartilage damage. The proinflammatory cytokines in normal BAT-transplanted mice, such as IL-12, IL-17, IL-6, and tumor necrosis factor-α (TNF-α), tended to decrease. Microarray analysis showed that the PI3K-AKT signaling pathway and IL-17 levels of CIA BAT tissues were significantly higher than those of normal BAT tissues. These results suggest that the transplantation of normal brown fat may have a therapeutic effect in RA patients.
