Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats

Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets

Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity.

The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress

Epitaxial growth of perovskite oxide films facilitated by oxygen vacancies

The authors would like to thank P. Yudin for valuable discussions, N. Nepomniashchaia for VASE studies, and S. Cichon for XPS analysis. The authors acknowledge support from the Czech Science Foundation (Grant No. 19-09671S), the European Structural and Investment Funds and the Ministry of Education, Youth and Sports of the Czech Republic through Programme ‘‘Research, Development and Education’’ (Project No. SOLID21 CZ.02.1.01/0.0/0.0/16-019/0000760), and ERA NET project Sun2Chem (E. K. and L. R.). Calculations have been done on the LASC Cluster in the ISSP UL.Single-crystal epitaxial films of technologically important and scientifically intriguing multifunctional ABO3 perovskite-type metal oxides are essential for advanced applications and understanding of these materials. In such films, a film-substrate misfit strain enables unprecedented crystal phases and unique properties that are not available in their bulk counterparts. However, the prerequisite growth of strained epitaxial films is fundamentally restricted by misfit relaxation. Here we demonstrate that introduction of a small oxygen deficiency concurrently stabilizes epitaxy and increases lattice strain in thin films of archetypal perovskite oxide SrTiO3. By combining experimental and theoretical methods, we found that lattice distortions around oxygen vacancies lead to anisotropic local stresses, which interact with the misfit strain in epitaxial films. Consequently, specific crystallographic alignments of the stresses are energetically favorable and can facilitate epitaxial growth of strained films. Because anisotropic oxygen-vacancy stresses are inherent to perovskite-type and many other oxides, we anticipate that the disclosed phenomenon of epitaxial stabilization by oxygen vacancies is relevant for a very broad range of functional oxides.This work is licensed under CC BY, CC BY-NC licenses.Czech Science Foundation (Grant No. 19-09671S); European Structural and Investment Funds and the Ministry of Education, Youth and Sports of the Czech Republic through Programme ‘‘Research, Development and Education’’ (Project No. SOLID21 CZ.02.1.01/0.0/0.0/16-019/0000760), and ERA NET project Sun2Chem; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART²

The Politics of the Communications Revolution in Western Europe

Pyruvate carboxylase (PC) plays a crucial role in various metabolic pathways, including gluconeogenesis, lipogenesis, and glucose-induced insulin secretion. Here we showed for the first time that the PC gene is transcriptionally regulated by peroxisome proliferator-activated receptor-γ (PPARγ) in vitro and in vivo in white and brown adipose tissue. PC mRNA and protein are markedly increased during differentiation of 3T3-L1 cells and HIB-1B, in parallel with the expression of the adipogenic transcription factors, CCAAT-enhancer binding protein α, PPARγ1, and PPARγ2. Tumor necrosis factor-α, a cytokine that blocks differentiation of 3T3-L1 cells, suppressed PC expression. Co-transfection studies in 3T3-L1 preadipocytes or HEK293T cells with a 2.3-kb promoter fragment of mouse PC gene linked to a luciferase reporter construct and with plasmids overexpressing retinoid X receptor α/PPARγ1 or retinoid X receptor α/PPARγ2 showed a 6-8-fold increase above the basal promoter activity. Furthermore, treatment of these transfected cells with the PPARγ agonist doubled the promoter activity. Mutation of the putative PPAR-response element-(-386/-374) of this 2.3-kb PC promoter fragment abolished the PPARγ response. Gel shift and chromatin immunoprecipitation assays demonstrated that endogenous PPARy binds to this functional PPAR-response element of the PC promoter. Mice with targeted disruption of the PPARγ2 gene displayed ∼50-60% reduction of PC mRNA and protein in white adipose tissue. Similarly, in brown adipose tissue of PPARγ2-deficient mice subjected to cold exposure, PC mRNA was 40% lower than that of wild type mice. Impaired in vitro differentiation of white adipocytes of PPARγ2 knock-out mice was also associated with a marked reduction of PC mRNA. Our findings identified PC as a PPARγ-regulated gene and suggested a role for PPARγ regulating intermediary metabolism.</p

Weight curves of rats on the control diet (circles, fed ad libitum), compared to the three experimental diets (iso-energetic pair feeding): low-carbohydrate high-fat, low-protein diet (LC-HF-LP; squares), low-carbohydrate high-fat, normal-protein diet (LC-HF-NP; upward triangles) or high fat diet (downward triangles); p<0.0005, repeated measurements ANOVA.

<p>The cumulative average weight gain for each group during the four week feeding period is given in the insert, analyzed by global one-way ANOVA and Dunnett tests for pairwise comparison vs. control: * p<0.05, *** p<0.001. Data are shown as means±SEM; n = 7 animals/group.</p

Respirometry.

<p>Measurement of mitochondrial oxygen consumption using microplate based extracellular flux analyzer in tissues from rats fed the control or experimental diets (LC-HF-LP, LC-HF-NP). A: brown adipocyte mitochondria. B: muscle mitochondria. Stage II, basal; stage III, ADP; stage IVo, oligomycin. N = 3/group.</p

Weight of interscapular brown adipose tissue (iBAT) in rats fed control or experimental diets (LC-HF-LP, LC-HF-NP, high fat).

<p>A: total weight (absolute); B: percentage of body weight (relative). Data are shown as means±SEM, n = 7/group; analyzed by global one-way ANOVA and Dunnett tests for pairwise comparison vs. control. * p<0.05, ** p<0.01 vs. control.</p

In-vivo measurement of maximal adaptive thermogenic capacity in rats fed the control or experimental diets (LC-HF-LP, LC-HF-NP, high fat).

<p>A: respiratory quotient after feeding control or experimental diets for 4 weeks: basal and following norepinephrine injection. B: Basal and norepinephrine stimulated energy expenditure (EE), expressed as kcal/h/kg BW^0.75. The time points 0 min and 36 min are not given, as cages had to be opened for animal handling and measures of RQ and EE are not reliable at these time points. The insert shows the mean EE of timepoints 77, 84 and 91 min. Data are shown as means±SEM; n = 7 (control), 6 (LC-HF-LP), 5 (LC-HF-NP), 7 (high fat). Statistical analysis was performed on the average of three time points at baseline and during the plateau phase after NE injection, respectively, using global one-way ANOVA and Dunnett tests for pairwise comparison vs. control.</p