Mice treated with TSLP cytokine lose weight by ‘sweating’ fat

rockarolla

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Another nail in CICO coffin:


Treating obese mice with the cytokine known as TSLP led to significant abdominal fat and weight loss compared to controls, according to new research published Thursday in Science from researchers in the Perelman School of Medicine at the University of Pennsylvania. Unexpectedly, the fat loss was notassociated with decreased food intake or faster metabolism. Instead, the researchers discovered that TSLP stimulated the immune system to release lipids through the skin's oil-producing sebaceous glands.

"This was a completely unforeseen finding, but we've demonstrated that fat loss can be achieved by secreting calories from the skin in the form of energy-rich sebum," said principal investigator Taku Kambayashi, MD, PhD,an associate professor of Pathology and Laboratory Medicine at Penn, who led the study with fourth-year medical student Ruth Choa, PhD. "We believe that we are the first group to show a non-hormonal way to induce this process, highlighting an unexpected role for the body's immune system."
The animal model findings, Kambayashi said, support the possibility that increasing sebum production via the immune system could be a strategy for treating obesity in people.
...
Given the dramatic results, Kambayashi assumed that the TSLP was sickening the mice and reducing their appetites. However, after further testing, his group found that the TSLP-treated mice were actually eating 20 to 30 percent more, had similar energy expenditures, base metabolic rates, and activity levels, when compared to their non-treated counterparts.
 

rockarolla

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I suspected for a long time that endotoxins are generally net pro metabolic, and their antagonists(TLR4 blockers) are anti.


1628611258113.png

TSLP is produced in macrophages. (A) RAW 264.7 cells were stimulated with LPS(endotoxin) or E. coli for 24 h. (A, upper panel) Cell viability was analyzed by an MTT assay. (A, lower panel) NO concentration was measured by the Griess method. (B,C) Cells were stimulated with LPS or E. coli (upper panel) for 24 h for ELISA or ( lower panel) 8 h for real -time PCR. Data are representative of three independent experiments (n = 5/group). A p value indicates the significant difference between PBS and LPS. LPS, lipopolysaccharide; TSLP, thymic stromal lymphopoietin; NO, nitric oxide.

(c) (PDF) TSLP Exacerbates Septic Inflammation via Murine Double Minute 2 (MDM2) Signaling Pathway
 

rockarolla

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Yet another nail ;)

Endotoxin Tolerance Is Associated With Reduced Secretion of Tumor Necrosis Factor
Endotoxin Tolerance Is Associated With Reduced Secretion of Tumor Necrosis Factor
Bacterial endotoxin effects are partially mediated by tumor necrosis factor (TNF). It is known that sublethal doses of endotoxin induce transient refractoriness (tolerance) to some of its effects. We studied the role of TNF in endotoxin tolerance in rats. Weight loss, lethality, and TNF production were measured after an initial dose of endotoxin and after subsequent doses. Weight loss reached its peak 72 hours after the initial endotoxin challenge, followed by recovery even under continued administration of endotoxin. While tolerant, rats could survive a dose of endotoxin that was lethal for 100% of naive rats. The high serum levels of TNF, observed 90 minutes after the first dose of endotoxin, markedly diminished when rechallenged during tolerance. Recovery of responsiveness to these effects followed the refractory phase by 3 weeks. We concluded that endotoxin tolerance is associated with a reduced secretion of TNF.


PAq40Jl.png
 

tankasnowgod

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Another nail in CICO coffin:


Treating obese mice with the cytokine known as TSLP led to significant abdominal fat and weight loss compared to controls, according to new research published Thursday in Science from researchers in the Perelman School of Medicine at the University of Pennsylvania. Unexpectedly, the fat loss was notassociated with decreased food intake or faster metabolism. Instead, the researchers discovered that TSLP stimulated the immune system to release lipids through the skin's oil-producing sebaceous glands.

Really? Please explain how "sweating it out" wouldn't fall under the "Calories Out" portion of the equation.
 

rockarolla

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Blunting the response to endotoxin in healthy subjects: Effects of various doses of intravenous fish oil​


To test the dose response effect of infused fish oil (FO) rich in n-3 PUFAs on the inflammatory response to endotoxin (LPS) and on membrane incorporation of fatty acids in healthy subjects. Prospective, sequential investigation comparing three different FO doses. Three groups of male subjects aged 26.8 +/- 3.2 years (BMI 22.5 +/- 2.1). One of three FO doses (Omegaven10%) as a slow infusion before LPS: 0.5 g/kg 1 day before LPS, 0.2 g/kg 1 day before, or 0.2 g/kg 2 h before. Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-alpha, stress hormones) were collected. After LPS temperature, ACTH and TNF-alpha concentrations increased in the three groups: the responses were significantly blunted (p < 0.0001) compared with the control group of the Pluess et al. trial. Cortisol was unchanged. Lowest plasma ACTH, TNF-alpha and temperature AUC values were observed after a single 0.2 g/kg dose of FO(fish oil). EPA incorporation into platelet membranes was dose-dependent. Having previously shown that the response to LPS was reproducible, this study shows that three FO doses blunted it to various degrees. The 0.2 g/kg perfusion immediately before LPS was the most efficient in blunting the responses, suggesting LPS capture in addition to the systemic and membrane effects.
 

rockarolla

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Our results showed that retinol suppressed the expression of various inflammatory cytokines in bone marrow-derived macrophages stimulated with ligands of TLR2, TLR3, or TLR4.

...


We report here that vitamin D3 [1alpha,25-dihydroxycholecalciferol, 1,25(OH)(2)D3] suppresses the expression of TLR2 and TLR4 protein and mRNA in human monocytes in a time- and dose-dependent fashion.
...
Our data provide strong evidence that 1,25(OH)(2)D3 primes monocytes to respond less effectively to bacterial cell wall components in a VDR-dependent mechanism, most likely due to decreased levels of TLR2 and TLR4.


Objectives. Recent studies have shown the immunomodulatory effect of vitamin D3 through down-regulation of Toll-like receptor (TLR) expression in human monocytes. To understand the implication of innate immunity with the role of vitamin D affecting TLR expression in Behçet's disease (BD), we focused on the association between the TLR expression and the serum vitamin D concentration in BD.

Methods. The expression of TLR2, TLR4 and CD16 on monocytes was detected by flow cytometric analysis and RT-PCR. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured in the patients with BD, psoriasis and healthy controls, and then the expression of TLRs was correlated with the value of serum 25(OH)D levels. To assess the influence of vitamin D3 on expression and function of TLRs in vitro, human monocytes were treated with increasing concentrations of 1,25(OH)2D3.

Results. We found that the monocytes of active BD patients showed higher expressions of TLR2 and TLR4 than those of controls, and serum 25(OH)D levels tended to be lower in active BD. Furthermore, 25(OH)D levels were inversely correlated with the expressions of TLR2, TLR4 and clinical indicators. In vitro analysis showed that vitamin D3 was found to dose-dependently suppress the protein and mRNA expressions of TLR2 and TLR4. TNF-α synthesis was also decreased upon TLR ligand stimulation in vitamin D3-treated monocytes.

Conclusion. These results suggest that the inflammation triggered through TLR2 and TLR4 is important in the pathogenesis of BD. And it seems possible that vitamin D may be used as a therapeutic option by modulating TLR2 and TLR4 expression of monocytes in BD.
 

rockarolla

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Um, no it's not. They are suggesting that fat would be excreted through the skin.

Its just a hypothesis - there is no 100% proof that the majority of calories are actually being excreted through skin due to elevated TSLPs. I.e. it could be an observable side effect.
 
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