scholarly journals Lactobacillus amylovorus KU4 ameliorates diet-induced obesity in mice by promoting adipose browning through PPARγ signaling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sung-Soo Park ◽  
Yeon-Joo Lee ◽  
Hyuno Kang ◽  
Garam Yang ◽  
Eun Jeong Hong ◽  
...  
Keyword(s):  
Probiotic Bacterium ◽  
Protective Effects ◽  
Diet Induced Obesity ◽  
White Adipocytes ◽  
Lactobacillus Amylovorus ◽  
Obesity In Mice ◽  
Lactate Levels ◽  
Transcriptional Complex ◽  
And Function

AbstractBrowning of white adipose tissue (WAT) is currently considered a potential therapeutic strategy to treat diet-induced obesity. While some probiotics have protective effects against diet-induced obesity, the role of probiotics in adipose browning has not been explored. Here, we show that administration of the probiotic bacterium Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD) enhanced mitochondrial levels and function, as well as the thermogenic gene program (increased Ucp1, PPARγ, and PGC-1α expression and decreased RIP140 expression), in subcutaneous inguinal WAT and also increased body temperature. Furthermore, LKU4 administration increased the interaction between PPARγ and PGC-1α through release of RIP140 to stimulate Ucp1 expression, thereby promoting browning of white adipocytes. In addition, lactate, the levels of which are elevated in plasma of HFD-fed mice following LKU4 administration, elicited the same effect on the interaction between PPARγ and PGC-1α in 3T3-L1 adipocytes, leading to a brown-like adipocyte phenotype that included enhanced Ucp1 expression, mitochondrial levels and function, and oxygen consumption rate. Together, these data reveal that LKU4 facilitates browning of white adipocytes through the PPARγ-PGC-1α transcriptional complex, at least in part by increasing lactate levels, leading to inhibition of diet-induced obesity.

The Role of the CX3CL1-CX3CR1 Axis in Renal Disease

2021 ◽  
Author(s):  
Diana Hamdan ◽  
Lisa A. Robinson
Keyword(s):  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Transmembrane Protein ◽  
Soluble Form ◽  
Protective Effects ◽  
Chronic Kidney Diseases ◽  
The Family ◽  
Soluble Species ◽  
And Function

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

Abstract 19727: ROCK2 Mediates Browning of White Fat and Protects Against Obesity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Phetcharat Chen ◽  
Christina Park ◽  
Eltayeb Karrar ◽  
Chaoyung Wang ◽  
James Liao
Keyword(s):  
Weight Gain ◽  
Body Temperature ◽  
Cold Exposure ◽  
Diet Induced Obesity ◽  
Therapeutic Benefits ◽  
White Adipocytes ◽  
Important Regulator ◽  
And Function ◽  
White Fat ◽  
Adipocyte Development

Background: The Rho-activated kinases (ROCK1 and ROCK2) are serine threonine kinases that are ubiquitously expressed with higher levels of ROCK2 compared to ROCK1 in adipocytes. Recent studies suggest that ROCK2 may be an important regulator of energy metabolism and obesity. However, its role in adipocyte development and function is unknown. Methods and Result: To determine the role of ROCK2 in adipocyte development and obesity, we generated adipocyte-specific deletion (ROCK2 adipoQ-/- ) and overexpression (CA-ROCK adipoQ+/+ ) of ROCK2 in mice. Compared to control mice, CA-ROCK adipoQ+/+ mice exhibited increased browning of inguinal white adipose tissue (iWAT). Indeed, immunohistochemical staining of iWAT in CA-ROCK adipoQ+/+ mice showed that UCP1 was upregulated. Furthermore, CA-ROCK adipoQ+/+ mice on high fat diet were resistant to weight gain and obesity for up to 18 weeks. This is in contrast to ROCK2 adipoQ-/- mice, which developed more weight gain or obesity than control mice. To determine the physiological effects of ROCK2 on browning of iWAT, control and ROCK2 adipoQ-/- mice were exposed to 4°C for 1 week. In control mice, cold exposure increased ROCK2 activity and lead to browning of iWAT. However, the iWAT in ROCK2 adipoQ-/- mice failed to undergo browning. Analysis of gene expression in iWAT demonstrated increased UCP1 and mitochondria proteins in control but not ROCK2 adipoQ-/- mice. Thermal imaging revealed that ROCK2 adipoQ-/- mice were unable to maintain basal body temperature after prolonged cold exposure. In contrast, the heat map of the CA-ROCK adipoQ+/+ mice showed an elevation of body temperature, particularly in areas of iWAT as compared to that of control littermates. Conclusions: ROCK2 mediates the “browning” of white adipocytes and prevents the development of obesity through increased thermogenesis. These findings suggest that the activation of ROCK2 in adipocytes may have therapeutic benefits in preventing diet-induced obesity.

scholarly journals Nicotinamide Nucleotide Transhydrogenase (Nnt) is Related to Obesity in Mice

2020 ◽  
Vol 52 (12) ◽  
pp. 877-881
Author(s):  
Anne Kunath ◽  
John T. Heiker ◽  
Matthias Kern ◽  
Joanna Kosacka ◽  
Gesine Flehmig ◽  
...  
Keyword(s):  
Fat Mass ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Wild Type ◽  
Inner Mitochondrial Membrane ◽  
Nicotinamide Nucleotide Transhydrogenase ◽  
Diet Induced Obesity ◽  
Highly Sensitive ◽  
Obesity In Mice

AbstractThe C57BL/6J (B6J) mouse strain has been widely used as a control strain for the study of metabolic diseases and diet induced obesity (DIO). B6J mice carry a spontaneous deletion mutation in the nicotinamide nucleotide transhydrogenase (Nnt) gene eliminating exons 7–11, resulting in expression of a truncated form of Nnt, an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this mutation in B6J mice is associated with epigonadal fat mass and altered sensitivity to diet induced obesity. To define the role of Nnt in the development of diet induced obesity, we generated first backcross (BC1) hybrids of wild type Nnt C57BL/6NTac and mutated Nnt C57BL/6JRj [(C57BL/6NTac×C57BL/6JRj)F1×C57BL/6NTac]. Body weight gain and specific fat-pad depot mass were measured in BC1 hybrids under high fat diet conditions. Both sexes of BC1 hybrids indicate that mice with Nnt wild type allele are highly sensitive to DIO and exhibit higher relative fat mass. In summary, our data indicate that the Nnt mutation in mice is associated with sensitivity to DIO and fat mass.

scholarly journals L-Theanine Activates the Browning of White Adipose Tissue through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-induced Obesity in Mice

2021 ◽  
Author(s):  
Wan-Qiu Peng ◽  
Gang Xiao ◽  
Bai-Yu Li ◽  
Ying-Ying Guo ◽  
Liang Guo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Intraperitoneal Administration ◽  
Dna Demethylation ◽  
Active Dna Demethylation ◽  
Diet Induced Obesity ◽  
Elevated Expression ◽  
Obesity In Mice

L-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with L-Theanine(100mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1 and other thermogenic genes. Meanwhile, administration of the mice with L-Theanine increased energy expenditure. In vitro studies indicated that L-Theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of L-Theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. L-Theanine treatment enhanced AMPKα phosphorylation both in adipocytes and in iWAT. Knockdown of AMPKα ablolished L-Theanine-induced upregulation of Prdm16 and adipocytes browning. L-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for L-Theanine-induced increase of α-KG and DNA demethylation on Prdm16 promoter. Moreover, intraperitoneal administration with L-Theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol and free fatty acid in the high fat diet-fed mice. Our results suggest a potential role of L-Theanine in combating diet-induced obesity in mice, which may involve L-Theanine-induced browning of white adipose tissue.

scholarly journals The Role of Regulatory B cells in Kidney Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Wang Long ◽  
Hedong Zhang ◽  
Wenjia Yuan ◽  
Gongbin Lan ◽  
Zhi Lin ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Diseases ◽  
Kidney Diseases ◽  
Specific Marker ◽  
Protective Effects ◽  
Regulatory B Cells ◽  
Multiple Phenotypes ◽  
Therapeutic Value ◽  
And Function

B cells, commonly regarded as proinflammatory antibody-producing cells, are detrimental to individuals with autoimmune diseases. However, in recent years, several studies have shown that regulatory B (Breg) cells, an immunosuppressive subset of B cells, may exert protective effects against autoimmune diseases by secretion of inhibitory cytokines such as IL-10. In practice, Breg cells are identified by their production of immune-regulatory cytokines, such as IL-10, TGF-β, and IL-35, however, no specific marker or Breg cell-specific transcription factor has been identified. Multiple phenotypes of Breg cells have been found, whose functions vary according to their phenotype. This review summarizes the discovery, phenotypes, development, and function of Breg cells and highlights their potential therapeutic value in kidney diseases.

Protective role of adipocyte hypoxia-inducible factor-2 in diet-induced obesity in mice

2014 ◽  
Vol 122 (03) ◽  
Author(s):  
R Garcia Martin ◽  
MF Rubín de Celis ◽  
A Ziogas ◽  
J Phieler ◽  
N Qin ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Protective Role ◽  
Diet Induced Obesity ◽  
Obesity In Mice

scholarly journals Mucin-derived O-glycans supplemented to diet mitigate diverse microbiota perturbations

2020 ◽  
Author(s):  
K. M. Pruss ◽  
A. Marcobal ◽  
A. M. Southwick ◽  
D. Dahan ◽  
S. A. Smits ◽  
...  
Keyword(s):  
Potential Role ◽  
In Silico Analysis ◽  
Enteric Pathogens ◽  
Microbiota Composition ◽  
Diet Induced Obesity ◽  
Porcine Gastric Mucin ◽  
And Function ◽  
Host Development ◽  
Silico Analysis

Abstract Microbiota-accessible carbohydrates (MACs) are powerful modulators of microbiota composition and function. These substrates are often derived from diet, such as complex polysaccharides from plants or human milk oligosaccharides (HMOs) during breastfeeding. Host-derived mucus glycans on gut-secreted mucin proteins serve as a continuous endogenous source of MACs for resident microbes; here we investigate the potential role of purified, orally administered mucus glycans in maintaining a healthy microbial community. In this study, we liberated and purified O-linked glycans from porcine gastric mucin and assessed their efficacy in shaping the recovery of a perturbed microbiota in a mouse model. We found that porcine mucin glycans (PMGs) and HMOs enrich for taxonomically similar resident microbes. We demonstrate that PMGs aid recovery of the microbiota after antibiotic treatment, suppress Clostridium difficile abundance, delay the onset of diet-induced obesity, and increase the relative abundance of resident Akkermansia muciniphila. In silico analysis revealed that genes associated with mucus utilization are abundant and diverse in prevalent gut commensals and rare in enteric pathogens, consistent with these glycan-degrading capabilities being selected for during host development and throughout the evolution of the host–microbe relationship. Importantly, we identify mucus glycans as a novel class of prebiotic compounds that can be used to mitigate perturbations to the microbiota and provide benefits to host physiology.

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