Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction
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PROVIDER: PRJNA1168174 | ENA |
REPOSITORIES: ENA
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Project description:Calorie restriction (CR) improves health and longevity. CR induces a periodic fasting cycle in mammals; our study compares CR with unanticipated fasting (F), when the food is unexpectedly withheld. F induces hepatic steatosis, while CR reduces it; surprisingly, the difference is not due to hepatic β-oxidation. Liver transcriptome analysis identifies fatty acid transporters (Slc27a1 and Slc27a2), TAG synthesis (Gpat4), and lipid storage (Plin2 and Cidec) genes to be upregulated only in F in agreement with hepatic steatosis. The circadian clock and anticipated fasting contribute to preventing fasting-associate hepatic steatosis in CR. Mechanistically, Slc27a1, Plin2 and Cidec genes are upregulated, and liver TAGs accumulate in circadian clock mutant mice on CR or if wild type CR mice miss their anticipated meal. The results highlight similarities and differences between unanticipated fasting and CR, suggesting that circadian clock dependent gating of transcriptional response to fasting controls lipid homeostasis and prevents hepatic steatosis.
2025-07-18 | GSE278669 | GEO
Project description:Investigated bone marrow metabolism in response to acute overnutrition (high calorie diet) and calorie deprivation (fasting). Bone marrow serum and peripheral serum were collected before and after each dietary intervention. Using proteomics analyses of the sera, we characterized nutritional influences on the local and systemic environments. In brief, proteomic analysis of the bone marrow serum after high calorie diet showed an upregulation of proteins related to an inflammatory/complement pathway, while bone marrow serum after fasting showed a significant downregulation of inflammatory/complement pathway proteins. In contrast, the peripheral serum showed signs of an increased inflammatory response that may be due to a rapid increase in body weight and fat mass seen in participants after 10 days of a high calorie diet. After fasting, peripheral serum did show a strong inflammatory response, but there was evidence of increased lipid biosynthesis. Overall, our results demonstrate key differences in inflammatory response and lipid metabolism between high calorie diet and fasting, despite a nearly identical bone marrow adipose phenotype.
2025-07-14 | PXD063552 | Pride
Project description:Expansion of bone marrow adipocytes has been linked to nutritional pressures, suggesting that bone marrow is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here we investigated bone marrow metabolism in response to acute overnutrition (high calorie diet) and calorie deprivation (fasting). Participants underwent a 10-day high calorie diet followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting. Bone marrow adipocytes were collected before and after each dietary intervention. Using RNA-sequencing, we characterized nutritional influences on bone marrow adiposity. Bone marrow adipocytes after high calorie diet showed an upregulation of FOXP3 (p < 0.0001), the transcription factor that controls the development of Tregs, which are critical in reducing inflammatory immune responses. In contrast, bone marrow adipocytes after acute fasting had an upregulation of inflammatory genes (CP, CFH, and IGFBP3) (p < 0.0001). Overall, our results demonstrate key differences in inflammatory responses between high calorie diet and fasting, despite a nearly identical phenotype of bone marrow adipose tissue expansion. Further analyses are needed to understand the effects nutritional pressures have on bone marrow adipogenesis and immune responses.
2025-05-24 | GSE297963 | GEO
Project description:BCL6 de-repression induces the fasting transcriptome and protects from steatosis
| PRJNA486799 | ENA
Project description:Caloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling Growing evidence supports an anti-lipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin deficient ob/ob mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction in leptin deficiency. Echocardiography was performed on C57Bl/6 wild-type mice (WT) and 7-month-old ob/ob mice fed ad lib, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for four weeks. Ventricular tissue was examined by electron microscopy (EM), mitochondrial coupling assay, and microarray expression profiling. LR and CR-ob/ob mice showed decreased body weight, heart weight, and LV wall thickness compared to ad lib ob/ob mice. LV fractional shortening was decreased in ad lib ob/ob mice, but restored to WT levels in LR and CR groups. However, EM revealed severe cardiac steatosis in the CR-ob/ob group compared to only moderate steatosis in ad lib ob/ob . Despite marked cardiac steatosis, CR (like LR) restored mitochondrial coupling to WT levels. CR up-regulated genes associated with oxidative stress and cell death, changes suggestive of cardiac lipotoxicity. LR, but not CR was shown to induce core genes involved in glycerolipid/free fatty acid cycling, a highly thermogenic pathway that can reduce intracellular lipid stores. LR, but not CR up-regulated and restored PGC1 and PPARto wild type levels; CR paradoxically further suppressed cardiac PPAR. Thus, leptin is essential in protecting the heart from lipotoxicity, and the inability to up-regulate the thermogenic glycerolipid/free fatty acid cycling pathway may impair the response of leptin deficient animals to the lipotoxic stress of calorie restriction. 6 month aged ob/ob mice were either leptin repleted with osmotic mini-pumps, calorie restricted to match the caloric intake of the leptin repleted mice, or fed ad lib for one month. 6-8 month C57Bl/6J mice were aged to serve as controls.
2011-04-29 | E-GEOD-16790 | biostudies-arrayexpress
Project description:BCL6 de-repression induces the fasting transcriptome and protects from steatosis (RNA-Seq)
| PRJNA486801 | ENA
Project description:BCL6 de-repression induces the fasting transcriptome and protects from steatosis (ChIP-Seq II)
| PRJNA533144 | ENA
Project description:BCL6 de-repression induces the fasting transcriptome and protects from steatosis (ChIP-Seq I)
| PRJNA486802 | ENA
Project description:Caloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling Growing evidence supports an anti-lipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin deficient ob/ob mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction in leptin deficiency. Echocardiography was performed on C57Bl/6 wild-type mice (WT) and 7-month-old ob/ob mice fed ad lib, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for four weeks. Ventricular tissue was examined by electron microscopy (EM), mitochondrial coupling assay, and microarray expression profiling. LR and CR-ob/ob mice showed decreased body weight, heart weight, and LV wall thickness compared to ad lib ob/ob mice. LV fractional shortening was decreased in ad lib ob/ob mice, but restored to WT levels in LR and CR groups. However, EM revealed severe cardiac steatosis in the CR-ob/ob group compared to only moderate steatosis in ad lib ob/ob . Despite marked cardiac steatosis, CR (like LR) restored mitochondrial coupling to WT levels. CR up-regulated genes associated with oxidative stress and cell death, changes suggestive of cardiac lipotoxicity. LR, but not CR was shown to induce core genes involved in glycerolipid/free fatty acid cycling, a highly thermogenic pathway that can reduce intracellular lipid stores. LR, but not CR up-regulated and restored PGC1-alpha and PPAR-alpha to wild type levels; CR paradoxically further suppressed cardiac PPAR-alpha. Thus, leptin is essential in protecting the heart from lipotoxicity, and the inability to up-regulate the thermogenic glycerolipid/free fatty acid cycling pathway may impair the response of leptin deficient animals to the lipotoxic stress of calorie restriction.
2011-04-29 | GSE16790 | GEO
Project description:The metabolic syndrome represents a cluster of well-documented risk factors for the development of type 2 diabetes and cardiovascular disease. Next to visceral obesity, dyslipidemia and insulin resistance, excessive triglyceride accumulation in the liver has been implicated to play a role in the development of the metabolic syndrome. To investigate the underlying molecular changes leading to hepatic steatosis we performed microarray analysis on livers of mice either fasted over night or fed a high fat diet for 2 Weeks. We analysed 7 500 genes and subsequently performed a pathway analysis to identify changes in hepatic genes in both models. Fasting induced a high number of differentially expressed hepatic genes, resulting in an change towards an energy saving phenotype. In contrast only a small number of genes were differentially expressed after high fat diet. Fasting promoted gluconeogenesis and b-oxidation, strongly suppressed cholesterol synthesis and activated pathways to preserve hepatic function. High fat diet induced steatosis was accompanied by the activation of the stearoyl-CoA desaturase and the lipogenic transcription factor Srebp-1c, both implicated in the development of hepatic insulin resistance. These changes reflect the activation of different gene expression programs in response to plasma lipid overload. Keywords: Diet intervention Two conditions, fasting and high fat diet. 5 biological replicates for comparison of high fat diet versus fasting and controls versus high fat diet, 4 biological replicates for the comparison of controls versus fasting. All biological replicates are performed as technical replicates in the form of a dye-swap. Total number of arrays hybridises is therefore 28.
2011-04-02 | E-GEOD-8576 | biostudies-arrayexpress