Gut microbiota deficient mice demonstrate accelerated glucose clearance. However, which tissues are responsible for the upregulated glucose uptake remains unresolved, with different studies ...suggesting that browning of white adipose tissue, or modulated hepatic gluconeogenesis, may be related to enhanced glucose clearance when the gut microbiota is absent. Here, we investigate glucose uptake in 22 different tissues in 3 different mouse models. We find that gut microbiota depletion via treatment with antibiotic cocktails (ABX) promotes glucose uptake in brown adipose tissue (BAT) and cecum. Nevertheless, the adaptive thermogenesis and the expression of uncoupling protein 1 (UCP1) are dispensable for the increased glucose uptake and clearance. Deletion of Ucp1 expressing cells blunts the improvement of glucose clearance in ABX-treated mice. Our results indicate that BAT and cecum, but not white adipose tissue (WAT) or liver, contribute to the glucose uptake in the gut microbiota depleted mouse model and this response is dissociated from adaptive thermogenesis.
The relation between gut microbiota and the host has been suggested to benefit metabolic homeostasis. Brown adipose tissue (BAT) and beige adipocytes facilitate thermogenesis to maintain host core ...body temperature during cold exposure. However, the potential impact of gut microbiota on the thermogenic process is confused. Here, we evaluated how BAT and white adipose tissue (WAT) responded to temperature challenges in mice lacking gut microbiota. We found that microbiota depletion via treatment with different cocktails of antibiotics (ABX) or in germ-free (GF) mice impaired the thermogenic capacity of BAT by blunting the increase in the expression of uncoupling protein 1 (UCP1) and reducing the browning process of WAT. Gavage of the bacterial metabolite butyrate increased the thermogenic capacity of ABX-treated mice, reversing the deficit. Our results indicate that gut microbiota contributes to upregulated thermogenesis in the cold environment and that this may be partially mediated via butyrate.
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•Mice lacking gut microbiota have impaired UCP1-dependent thermogenesis in cold•These effects are replicated in germ-free mice treated with CL-316243•IL-4 has no differential effect on energy metabolism in either control or ABX mice•Gavage of ABX mice with butyrate partially rescues the effects on BAT recruitment
Li et al. use different antibiotic recipes and germ-free mice to demonstrate the dependence of UCP1-dependent thermogenesis in the cold on the presence of a healthy gut microbiome. Gavage with butyrate partly rescues the effect, indicating a role for this molecule in normal thermogenic responses to low temperature.
The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1% to 20% protein combined with either 60% or ...20% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60% fat. Moreover, they did not show hyperphagia when returned to a 20% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.
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•Very low protein caused decreased body fat and improved glucose tolerance•Fatty acid and amino acid metabolism were changed by dietary low protein•The 1% protein group did not show hyperphagia despite the hunger pathway being activated•The effect of 1% protein on food intake was linked to hypothalamic mTOR signaling
Wu et al. investigated how very low levels of dietary protein affect energy balance by exposing mice to diets containing 1%–20% protein. Very low protein caused decreased food intake despite activated hunger signaling and led to decreased body weight, partially due to inhibited hypothalamic mTOR signaling but not eIF2a, TRPML1, and FGF21 signaling.
As the economic center and major grain-producing area in Southwest China, the calculation of the carbon budget and the protection of cultivated land in the Chengdu Plain are of vital significance for ...China to achieve a carbon peak strategy and ensure food security. For the purpose of clarifying the trend of land use focus and carbon emissions in the Chengdu Plain, the carbon peak level of land use in 33 counties in the Chengdu Plain was explored. Based on the gravity center model and IPCC carbon emission coefficient method, the changing trend of land use gravity center and carbon emission in Chengdu Plain from 2006 to 2022 was clarified. PLS regression model and LMDI model were used to explore the main influencing factors of the carbon emission of cropland and the carbon emission of building land. PLUS model was used to simulate future land use patterns and carbon emissions. (1) The center of gravity of cropland, building land, water, and other and unused land shifted to the northeast by 4.23 km, 5.46 km, 8.44 km, and 31.58 km, respectively, and that of forest and grass shifted to the southeast by 11.12 km and 3.41 km, respectively. For major food crops, the centers of gravity of rice and maize moved northeastward by 15.47 km and 7.52 km, respectively, while wheat moved southwestward by 17.77 km. (2) From 2006 to 2022, carbon emissions from land use in the 33 counties of the Chengdu Plain are all on the rise, with a total increase of 13.552 million tons, and carbon sinks in the 31 counties continue to decline, with a total decrease of 0.691 million tons. (3) Under the natural scenario, carbon sink scenario, and carbon reduction scenario, the carbon emissions from land use decrease by 0.5391 million tons, 3.4728 million tons, and 4.5265 million tons from 2022, respectively. Among the 33 counties in the Chengdu Plain, 11 counties did not achieve carbon peak under the natural scenario, 5 counties did not achieve carbon peak under the carbon sink scenario, and all the counties achieved carbon peak under the carbon sink scenario. During the study period, there was a serious loss of cropland in the Chengdu Plain, mainly to building land in the central part of the Chengdu Plain and to forests within the Longmen Mountain, Longquan Mountain, and Leshan City, and there is a need to strengthen cropland protection in this region in the future. Under the natural scenario, carbon sink scenario, and carbon reduction scenario, land use in the Chengdu Plain region can achieve carbon peak, and the carbon reduction model will be more helpful for the counties to achieve carbon peak.
Major depressive disorder has deleterious impacts on mood, cognition, and many functions of daily life. Even after remission of mood symptoms, patients frequently report persistent cognitive ...deficits. By contrast, the neurogenic theory of depression posits that recovery from depression is dependent upon a restoration of neurogenesis. The present study was designed to test this prediction by assessing performance in MDD in-patients on a broad battery of cognitive tasks including the Mnemonic Similarity Task, a high interference memory test that is a putative correlate of neurogenesis. We predicted that remitted patients should exhibit recovery of function on this task, even though they may show residual deficits on other cognitive tasks.
18 hospitalized patients diagnosed with MDD and 22 healthy control participants matched for age, sex, and education completed a battery of mood and cognitive tests at two time points. Patients completed their baseline assessments when first admitted to hospital and repeated the same assessments upon remission, typically 4-5 weeks later and just prior to their release from hospital. Control participants were tested at baseline and 4-5 weeks later on the same assessment battery, which included the BDI-II, BAI, Cohen's PSS, Mnemonic Similarity Task, and several sub-tests adapted from the CANTAB.
At baseline, MDD patients were impaired relative to controls on the MST and many other cognitive tasks. Upon remission, patients' MST scores did not differ from those of healthy controls, although patients were still impaired on Pattern Recognition Memory, Spatial Recognition Memory, Delayed Matching to Sample and Paired Associates Learning relative to healthy control participants.
The lingering memory deficits observed in remitted patients with MDD observed here are broadly consistent with findings in the literature. Importantly, however, remitted patients showed recovery of cognitive function on the Mnemonic Similarity Task. This is the first study that we are aware of to report recovery of function on a high interference, putatively neurogenesis-dependent memory test in a longitudinal sample of hospitalized MDD patients from admission to remission. Our findings are consistent with the neurogenic theory of depression, which posits that a restoration of neurogenesis is linked to recovery from depression.
Synaptic connections must be precisely controlled to ensure proper neural circuit formation. In Drosophila melanogaster, bone morphogenetic protein (BMP) promotes growth of the neuromuscular junction ...(NMJ) by binding and activating the BMP ligand receptors wishful thinking (Wit) and thickveins (Tkv) expressed in motor neurons. We report here that an evolutionally conserved, previously uncharacterized member of the S6 kinase (S6K) family S6K like (S6KL) acts as a negative regulator of BMP signaling. S6KL null mutants were viable and fertile but exhibited more satellite boutons, fewer and larger synaptic vesicles, larger spontaneous miniature excitatory junctional potential (mEJP) amplitudes, and reduced synaptic endocytosis at the NMJ terminals. Reducing the gene dose by half of tkv in S6KL mutant background reversed the NMJ overgrowth phenotype. The NMJ phenotypes of S6KL mutants were accompanied by an elevated level of Tkv protein and phosphorylated Mad, an effector of the BMP signaling pathway, in the nervous system. In addition, Tkv physically interacted with S6KL in cultured S2 cells. Furthermore, knockdown of S6KL enhanced Tkv expression, while S6KL overexpression downregulated Tkv in cultured S2 cells. This latter effect was blocked by the proteasome inhibitor MG132. Our results together demonstrate for the first time that S6KL regulates synaptic development and function by facilitating proteasomal degradation of the BMP receptor Tkv.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The carbohydrate-insulin model (CIM) predicts that increases in fasting and post-prandial insulin in response to dietary carbohydrates stimulate energy intake and lower energy expenditures, leading ...to positive energy balance and weight gain. The objective of the present study was to directly test the CIM's predictions using C57BL/6 mice.
Diets were designed by altering dietary carbohydrates with either fixed protein or fat content and were fed to C57BL/6 mice acutely or chronically for 12 weeks. The body weight, body composition, food intake, and energy expenditures of the mice were measured. Their fasting and post-prandial glucose and insulin levels were also measured. RNA-seq was performed on RNA from the hypothalamus and subcutaneous white adipose tissue. Pathway analysis was conducted using IPA.
Only the post-prandial insulin and fasting glucose levels followed the CIM's predictions. The lipolysis and leptin signaling pathways in the sWAT were inhibited in relation to the elevated fasting insulin, supporting the CIM's predicted impact of high insulin. However, because higher fasting insulin was unrelated to carbohydrate intake, the overall pattern did not support the model. Moreover, the hypothalamic hunger pathways were inhibited in relation to the increased fasting insulin, and the energy intake was not increased. The browning pathway in the sWAT was inhibited at higher insulin levels, but the daily energy expenditure was not altered.
Two of the predictions were partially supported (and hence also partially not supported) and the other three predictions were not supported. We conclude that the CIM does not explain the impact of dietary macronutrients on adiposity in mice.
•Higher fasting insulin related to inhibited lipolysis and leptin pathways in sWAT, supporting CIM.•Higher fasting insulin related to inhibited hypothalamic hunger pathway, contrasting CIM.•Fasting insulin decreased with higher dietary carbohydrate, overall contrasting CIM.•Higher dietary carbohydrate did not lead to greater EI/adiposity, or lowered EE.
A variety of inbred mouse strains have been used for research in metabolic disorders. Despite being inbred, they display large inter-individual variability for many traits like food intake and body ...weight. However, the relationship between dietary macronutrients and inter-individual variation in body weight and food intake of different mouse strains is still unclear. We investigated the association between macronutrient content of the diet and variations in food intake, body composition, and glucose tolerance by exposing five different mouse strains (C57BL/6, BALB/c, C3H, DBA/2, and FVB) to 24 different diets with variable protein, fat, and carbohydrate contents. We found only increasing dietary fat, but not protein or carbohydrate had a significant association (positive) with variation in both food intake and body weight. The highest variation in both body weight and food intake occurred with 50% dietary fat. However, there were no significant relationships between the variation in fat and lean mass with dietary protein, fat, or carbohydrate levels. In addition, none of the dietary macronutrients had significant impacts on the variation in glucose tolerance ability in C57BL/6 mice. In conclusion, the variations in food intake and body weight changes increased with the elevation of dietary fat levels.