Antiobesity Effect of Lacticaseibacillus paracasei LM-141 on High-Fat Diet-Induced Rats through Alleviation of Inflammation and Insulin Resistance.

In this study, we set out to evaluate the antiobesity activities of our newly isolated Lacticaseibacillus paracasei LM-141 (LPLM141) using a high-fat diet (HFD)-fed rat model. Male Sprague-Dawley rats were fed with a HFD with or without low-dosage (2 × 107 CFU/day per rat) or high-dosage (2 × 109 CFU/day per rat) LPLM141 for 14 weeks. The results showed that administration of LPLM141 significantly decreased body weight gain, liver weight, adipose tissue weight, and epididymal white adipocyte size increased by HFD feeding. The abnormal serum lipid profile induced by HFD feeding was normalized by administration of LPLM141. The enhanced chronic low-grade inflammation in HFD-fed rats was reduced by LPLM141 supplementation, as reflected by decreased serum lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) levels, reduced macrophage infiltration in adipose tissue, and increased serum adiponectin concentration. In addition, the elevations of proinflammatory cytokine genes and suppression of PPAR-γ mRNA in adipose tissues of rats fed with a HFD were markedly reversed by LPLM141 administration. Oral administration of LPLM141 induced browning of epididymal white adipose tissue (eWAT) and activation of interscapular brown adipose tissue (iBAT) in rats fed with HFD. Consumption of LPLM141 exhibited a significant amelioration in insulin resistance, which were mechanistically caused by downregulation of the serum leptin level and upregulation of hepatic IRS-1 and p-Akt protein expressions, in HFD treated rats. LPLM141 consumption significantly decreased hepatic lipogenic gene expressions and preserved liver function stimulated by HFD treatment. Administration of LPLM141 obviously mitigated hepatic steatosis observed in HFD feeding rats. Our current findings shed light on LPLM141 supplementation that exhibited an antiobesity effect in HFD-fed rats by alleviating inflammation and insulin resistance, which further highlighted the potential of utilizing LPLM141 as a preventive/therapeutic probiotic agent for obesity.

Effects of irradiance on UVA-induced skin aging.

BACKGROUND: Ultraviolet A (UVA) radiation is the most relevant component of solar radiation-induced skin aging. Sunscreens were used to minimize the harmful effects of UV radiation on our skin by reducing UV irradiance. We previously found that at equivalent fluence, UVB radiation at low irradiance (LI) has higher photocarcinogenic potential as compared to its high irradiance (HI) counterpart. OBJECTIVES: To examine the effects of equivalent fluence of UVA radiation administered at different irradiance on photoaging. METHODS: Both the hairless mice (SKH-1) and human dermal fibroblasts were irradiated with high irradiance UVA (HIUVA) or low irradiance UVA (LIUVA; 50% irradiance of HIUVA) at equivalent fluence. Parameters related to skin photoaging were evaluated. RESULTS: For hairless mice receiving equivalent fluence of UVA radiation, LIUVA treated mice showed prominent skin aging as compared to its HIUVA treated counterpart. In addition, LIUVA radiation induced higher reactive oxygen species (ROS) production and c-Jun N-terminal kinases (JNK) phosphorylation as compared to their HIUVA treated counterparts. Pretreatment with N-acetylcysteine (NAC) abrogate the difference between HI and LIUVA radiation on fibroblasts in terms of intracellular ROS, JNK phosphorylation, MMP-1 expression and type I collagen expression. CONCLUSION: UVA radiation administered at LI (a scenario similar to sunscreen use) led to more severe aging process as compared to its HI counterpart. Unexpected negative effect may be imposed on the skin if sunscreen use is accompanied by longer duration spent under the sun.

The effect of interaction of heat and UVB on human keratinocyte: Novel insights on UVB-induced carcinogenesis of the skin.

BACKGROUND: Skin cancer is an important environmentally-related health issue. Although sun exposure is closely associated with increasing environmental heat, the effects of environmental heat on the skin, especially in the context of photocarcinogenesis, has not been carefully examined. OBJECTIVES: This study aimed to explore the effects and interactions of UVB radiation and environmental heat on photocarcinogenesis of the skin using cell and animal models. METHODS: Cultured keratinocytes and hairless mice were exposed to different treatment conditions including UVB radiation and environmental heat. The effects of treatment on keratinocyte and mice skin were evaluated at indicated time points. RESULTS: UVB induced DNA damage was significantly lower in keratinocytes that were pretreated in an environment with slightly elevated temperature followed by UVB treatment (Heat-UVB) as compared to UVB and UVB radiation followed by exposure to equivalent increase in environmental heat (UVB-Heat) groups. Similar phenomenon was observed in terms of keratinocyte viability. In the animal model, it was found that Heat-UVB treated mice showed delayed and reduced tumor formation as compared to the UVB and UVB-Heat treated groups. Quantum simulation analyses demonstrated that the energy required for CPD formation at environment with higher temperature required considerable higher energy as compared to CPD formation at lower temperature. CONCLUSION: Taken together, our results demonstrated that with equivalent UVB exposure, higher temperature environment may protect cells against subsequent UVB-induced DNA damages.

Heat-killed and live Lactobacillus reuteri GMNL-263 exhibit similar effects on improving metabolic functions in high-fat diet-induced obese rats.

Our objective was to investigate and compare the effects of heat-killed (HK) and live Lactobacillus reuteri GMNL-263 (Lr263) on insulin resistance and its related complications in high-fat diet (HFD)-induced rats. Male Sprague-Dawley rats were fed with a HFD with either HK or live Lr263 for 12 weeks. The increases in the weight gain, serum glucose, insulin, and lipid profiles in the serum and liver observed in the HFD group were significantly reduced after HK or live Lr263 administration. Feeding HK or live Lr263 reversed the decreased number of probiotic bacteria and increased the number of pathogenic bacteria induced by high-fat treatment. The decreased intestinal barrier in the HFD group was markedly reversed by HK or live Lr263 treatments. The elevations of pro-inflammatory associated gene expressions in both adipose and hepatic tissues by high-fat administration were markedly decreased by HK or live Lr263 treatments. The increased macrophage infiltration noticed in adipose tissue after high-fat treatment was effectively suppressed by HK or live Lr263 consumption. The insulin resistance associated gene expressions in both adipose and hepatic tissues, which were downregulated in the HFD group, were markedly enhanced after HK or live Lr263 administration. HK or live Lr263 consumption significantly decreased hepatic lipogenic gene expressions stimulated by high-fat treatment. Administration of HK or live Lr263 significantly reduced hepatic oil red O staining and ameliorated the hepatic steatosis observed in high-fat treated rats. Our data suggested that similar to live Lr263, HK Lr263 exerted significant effects on attenuating obesity-induced metabolic abnormalities by reducing insulin resistance and hepatic steatosis formation.

High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human ß-Defensin-3 Expression [corrected] in Keratinocytes.

Diabetes mellitus is characterized by elevated plasma glucose and increased rates of skin infections. Altered immune responses have been suggested to contribute to this prevalent complication, which involves microbial invasion. In this study we explored the effects of a high-glucose environment on the innate immunity of keratinocytes by focusing on ß defensin-3 (BD3) using in vivo and in vitro models. Our results demonstrated that the perilesional skins of diabetic rats failed to show enhanced BD3 expression after wounding. In addition, high-glucose treatment reduced human BD3 (hBD3) expression of cultured human keratinocytes. This pathogenic process involved inhibition of p38MAPK signaling, an event that resulted from increased formation of advanced glycation end products. On the other hand, toll-like receptor-2 expression and function of cultured keratinocytes were not significantly affected by high-glucose treatment. In summary, high-glucose conditions inhibited the BD3 expression of epidermal keratinocytes, which in turn contributed to the frequent occurrences of infection associated with diabetic wounding.