Nós investigamos se o ácido palmitoléico modula o metabolismo de glicose e triacilglicerol (TAG) em adipócitos. Assim, células 3T3-L1 tratadas com ácido palmitoleico (16:1n7 , 200 mM) ou palmítico (16:0, 200 mM) por 24h e adipócitos epididimais de camundongos selvagem ou deficientes para PPARa tratados com 16:1n7 o ácido oleico (18:1n9, 300 mg / kg / dia), via gavagem durante 10 dias, foram avaliados. O tratamento com palmitoleico aumenta a captação de glicose e o conteúdo de GLUT4 e pThr172AMPKa. O aumento de GLUT4 foi abolido pela inibição da AMPK. Palmitoleico aumenta a conversão de glicose em lactato e CO2 e diminui a síntese de novo de ácidos graxos. O tratamento de células 3T3-L1 com ácido palmitoleico aumentou a lipólise o mRNA da ATGL e HSL, além do conteúdo proteico da ATGL e pSer660HSL. O aumento na lipólise foi abolido pela inibição de PPARa. Também, o tratamento de camundongos selvagens, mas não os deficientes para PPARa, com palmitoleico aumentou a lipólise e o mRNA da ATGL e HSL em adipócitos. Em resumo, o ácido palmitoleico aumenta a captação de glicose e sua utilização pelos adipócitos, um efeito que está associado com a expressão de GLUT4 e AMPK. Além disso, este ácido aumenta a lipólise e lipases em adipócitos viA PPARa. / We investigated whether palmitoleic acid modulates glucose and triacylglycerol (TAG) metabolism in white adipocytes. For this, 3T3-L1 cells treated with palmitoleic (16:1n7, 200 µM) or palmitic acid (16:0, 200 mM) for 24h and epididimal adipocytes from wild type or PPARa deficient mice treated with 16:1n7 or oleic acid (18:1n9, 300 mg/kg/day) by gavage for 10 days were evaluated. Thus, treatment with palmitoleic increases glucose uptake and the content of GLUT4 and pThr172AMPKa. The increase in GLUT4 was prevented by AMPK inhibition. Also, palmitoleic increases glucose conversion into lactate and CO2, and decreases de novo fatty acids synthesis. Furthermore, treatment of 3T3-L1 cells with palmitoleic increased lipolysis, mRNA levels of ATGL and HSL and protein content of ATGL and pSer660-HSL. Such increase in lipolysis can be prevented by PPARa inhibition. Treatment of wild type, but not PPARa deficient mice, with palmitoleic increased adipocytes lipolysis and ATGL and HSL mRNA levels. In conclusion, palmitoleic acid increases glucose uptake and utilization by adipocytes, associated with GLUT4 expression and AMPK activation. Furthermore, palmitoleic acid increases adipocyte lipolysis and lipases via PPARa.

Orientador: Eduardo Rochete Ropelle / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Aplicadas / Made available in DSpace on 2018-08-24T14:06:26Z (GMT). No. of bitstreams: 1 Pauli_LucianaSantosSouza_M.pdf: 2136192 bytes, checksum: ba071049e1cda0b7eb5230076d5d4b4e (MD5) Previous issue date: 2013 / Resumo: A proteína MKP-3 (MAPK phosphatase-3) possui capacidade de associar-se fisicamente e desfosforilar a FoxO1 no fígado, resultando em aumento da gliconeogênese e hiperglicemia na condição de obesidade e diabetes. Por outro lado, o exercício físico é uma das estratégias não farmacológicas mais utilizadas para a melhora do perfil glicêmico em pacientes diabéticos, no entanto, suas ações no tecido hepático são pouco conhecidas. Assim, o objetivo deste trabalho foi investigar os efeitos do treinamento físico sobre a expressão proteica da MKP-3, bem como sua interação com a FoxO1 em fígado de animais obesos. Ademais, tem como objetivo avaliar o mecanismo pelo qual o exercício físico é capaz de inibir a proteína MKP-3 em tecido hepático. Foram utilizados camundongos Swiss machos que receberam por 16 semanas uma dieta padrão ou rica em gordura. Os animais foram distribuídos aleatoriamente em seis grupos: controle (C), obeso sedentário (OB), obeso exercitado (EXE), obeso tratado com oligonucleotídeo antisense MKP-3 (OB-ASO), obeso tratado com sense MKP-3 (OB-sense) e obeso submetido ao treinamento físico e ao tratamento com antisense MKP-3 concomitantemente (OB-EXE-ASO). O protocolo de treinamento físico consistiu de natação com sessões de 60 minutos, 5 vezes por semana, com carga equivalente a 5% da massa corporal total do animal. O tratamento com antisense foi realizado através de injeções duas vezes ao dia, com um volume total de 2.0 ?l por dose (4.0 nmol/?l) por 5 dias. Ao final do experimento foram realizados os testes de tolerância ao piruvato (TTP) e teste de tolerância à insulina (TTI). Além disso, foram avaliados parâmetros fisiológicos (ingestão calórica, massa corporal, glicemia e insulinemia de jejum) e a análise molecular das proteínas (MKP-3, FoxO1, PGC1?, HNF-4?, PEPCK, G6Pase, ERK e CK2?) através das técnicas de imunoblot e imunoprecipitação. Utilizou-se a técnica de imunohistoquímica para análise da co-localização da MKP-3 no fígado dos animais. Os resultados obtidos demonstraram que o treinamento físico diminuiu expressão proteica de MKP-3 e a associação FoxO1/MKP-3 no fígado dos animais obesos. Além disso, camundongos obesos treinados apresentaram maiores níveis de FoxO1 fosforilada e diminuição da expressão das proteínas PGC-1? e HNF-4???no fígado se comparado aos animais obesos não submetidos ao treinamento físico. Verificam-se também menores níveis das enzimas gliconeogênicas PEPCK e G6Pase nos animais obesos treinados se comparado aos seus pares sedentários. Estes resultados a nível molecular foram acompanhados por alterações fisiológicas incluindo aumento da sensibilidade à insulina no fígado, menor produção hepática de glicose e redução da hiperglicemia nos camundongos obesos, independentemente da redução da massa corporal total. Ademais, não foram encontrados efeitos aditivos sobre os parâmetros fisiológicos e moleculares com o tratamento de oligonucleotídeo antisense MKP-3 e treinamento físico realizado concomitantemente nos animais obesos. Por fim, os efeitos supressivos do treinamento físico sobre a proteína MKP-3 parecem estar relacionados, no mínimo em parte, a diminuição na fosforilação das ERKs no fígado de camundongos obesos / Abstract: The protein MKP-3 (MAPK phosphatase-3) has the ability to physically associate with and dephosphorylate the FoxO1 in the liver, resulting in increased gluconeogenesis and hyperglycemia in the condition of obesity and diabetes. On the other hand, exercise is one of the most used non-pharmacological strategies for improving glycemic control in diabetic patients; however, their actions in liver tissue are poorly explored. The objective of this study was to investigate the effects of exercise on the expression of MKP-3 and its interaction with FoxO1 in the liver of obese animals. Furthermore, aimed at evaluating the mechanism by which physical exercise is able to inhibit protein MKP-3 in the liver. We used male Swiss mice that received a standard diet or high fat for 16 weeks. The animals were randomly divided into six groups: control (C), sedentary obese (OB), obese exercised (EXE), obese treated with MKP-3 antisense oligonucleotide (ASO-OB), obese treated with sense MKP-3 (OB- sense) and obese subjected to physical training and treatment with antisense MKP-3 concomitantly (OB-EXE-ASO). The protocol consisted of swimming exercise training with sessions of 60 minutes, five times per week with a load equivalent to 5% of the total body mass of the animal. Treatment with antisense was performed by injection twice daily, with a total volume of 2.0 ul per dose (4.0 nmol / microl) for 5 days. At the end of the experiment were performed to pyruvate tolerance tests (PTT) and insulin tolerance test (ITT). Furthermore, physiological parameters were evaluated (caloric intake, body weight, blood glucose and fasting insulin) and molecular analysis of proteins (MKP-3, FoxO1, PGC1a, HNF-4a PEPECK, G6Pase, ERK and CK2?) by immunoblotting and immunoprecipitation techniques. The immunohistochemistry technique was utilized to evaluate the co-localization of MKP-3 in the liver of the animals. The results showed that physical training decreased the protein expression of MKP-3 and association FoxO1/MKP-3. Further, trained obese mice had higher levels of phosphorylated FoxO1 and decreased PGC-1? and HNF-4??? There was also a decrease in the protein levels of PEPCK and G6Pase in the liver of mice exercised compared to sedentary obese mice. These results at molecular level were accompanied by physiological changes including increased insulin sensitivity in the liver, reduced hepatic glucose production and reduce hyperglycemia in obese mice, regardless of reducing total body mass. In addition, there were no additive effects of treatment with antisense oligonucleotide MKP-3 and physical training performed concurrently in obese animals. Finally, the suppressive effects of physical training on MKP-3 protein appear to be related at least in part, the decrease in phosphorylation of ERKs in the livers of obese mice / Mestrado / Metabolismo e Biologia Molecular / Mestra em Ciências da Nutrição e do Esporte e Metabolismo

Orientadores: Everardo Magalhães Carneiro, Camila Aparecida Machado de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-20T15:32:11Z (GMT). No. of bitstreams: 1 CostaJunior_JoseMaria_M.pdf: 1708636 bytes, checksum: 8f21b938177c9819646df6957696b6c4 (MD5) Previous issue date: 2012 / Resumo: Neste trabalho investigamos os efeitos do treinamento físico aeróbio de longa duração, associado ou não com a suplementação de leucina, sobre o metabolismo protéico e glicídico em músculo soleus de camundongos Swiss. Para isso, parte dos camundongos (T) realizou protocolo de 12 semanas de exercício de natação, com 1h de duração, 5 dias/semana, sem sobrecarga, e a outra parte permaneceu sedentária (C). Metade dos animais dos grupos C e T foram suplementados com leucina (1,5%) na água para beber (grupos CL e TL, respectivamente) ao longo do experimento. Os dados foram analisados pela ANOVA Two-Way (variáveis exercício e suplementação com leucina) e o teste post hoc de Newman-Keus foi empregado nos casos de interação das variáveis. Foi adotado um valor de p<0,05 como estatisticamente significativo. Resultados: A área abaixo da curva glicêmica durante o teste de tolerância à glicose foi maior nos grupos suplementados com leucina (CL e TL). Já a sensibilidade à insulina, estimada pelo kITT, foi maior por efeito do exercício. A fosforilação da AS160, etapa distal da cascata de sinalização que leva a captação de glicose no músculo, foi maior no grupo T em relação aos demais tanto na condição basal quanto estimulada com insulina, provavelmente via AMPK, cuja fosforilação foi maior por efeito do exercício em ambas as condições, mas diminuída por efeito da suplementação com leucina após estimulação com insulina. A fosforilação da Akt não foi afetada pelo exercício, mas foi menor no grupo CL em relação aos demais. Apesar do maior peso do músculo soleus por efeito do exercício, a síntese protéica não diferiu entre os grupos, mesmo com a maior fosforilação da mTOR na condição basal no grupo CL, e a redução por efeito do exercício após estimulação com insulina. A degradação protéica no referido músculo, contudo, foi reduzida por efeito do exercício. A expressão gênica de isoformas específicas de E2 e E3 ligases, integrantes da via proteolítica ubiquitina-proteossoma, também foi menor por efeito do exercício. Todos os indicadores de resposta ao treinamento aeróbio foram aumentados por efeito do exercício: tempo até a exaustão em teste de esforço, oconsumo máximo de oxigênio e atividade da enzima citrato sintase. Alguns destes indicadores também sofreram interferência da suplementação. Concluímos que a suplementação com leucina pode prejudicar a homeostase glicêmica e reduzir os efeitos positivos do exercício sobre a sinalização insulínica. O exercício aumentou o peso do músculo soleus ao diminuir a degradação protéica por inibição da via proteolítica ubiquitina-proteossomo, enquanto a síntese protéica não foi afetada por nenhum tratamento (exercício ou suplementação com leucina) / Abstract: We investigated the effects of chronic physical training, associated or not with leucine supplementation, on protein and glucose metabolism in soleus muscle of Swiss mice. Half of the mice (T) performed a 12 weeks protocol of swimming exercise, 1h/day, 5 days/week, bearing no overload, and the other half remained sedentary (C). Additionally, half of the C and T mice were supplemented with leucine (1,5%) into the drinking water (groups CL and TL, respectively) throughout the experiment. Data were analysed by Two-Way ANOVA (variables exercise and leucine supplementation) and the Newman-Keus post hoc test was used in the cases of interaction between the variables. A p<0,05 was considered statistically significant. Results: The area under glucose curve during glucose tolerance test was increased in the leucine supplemented groups (CL and TL). Insulin sensitivity, estimated by kITT, was higher as an effect of exercise. AS160 phosphorylation, a distal step in the signaling pathway which leads to muscle glucose uptake, was increased in the T group compared to the others in both basal and insulin-stimulated condition, probably via AMPK, whose phosphorylation was increased by exercise in both conditions, but it was reduced by an effect of leucine supplementation following insulin stimulation. Akt phosphorylation was not affected by exercise, but it was reduced in the CL group compared to the other groups. Despite the increased weight of soleus muscle caused by an effect of exercise, protein synthesis was similar among the groups, even with the increased mTOR phosphorylation at the basal condition in the CL group, and the reduction caused by exercise following insulin stimulation. Protein degradation in the soleus muscle was reduced by an effect of exercise. Gene expression of specific isoforms of E2 and E3 ligases, members of the ubiquitin-proteosome proteolytic pathway, was also reduced by an effect of exercise. All the indicators of response to aerobic training were increased by exercise: time to exhaustion in the effort test, maximal oxygen uptake and citrate synthase enzyme activity. Some of these indicators were also affected by leucine supplementation. We conclude that leucine supplementation may impair glucose homeostasis and reduce the positive effects of exercise on insulin signaling. Exercise increased soleus muscle weight by reducing protein degradation via an inhibition of the ubiquitin-proteasome proteolytic pathway, whereas protein synthesis was not affected by either of the treatments (exercise or leucine supplementation) / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

Abstract Estrogen replacement therapy (ERT) has been associated with favorable effects on risk factors for atherosclerosis. In observational studies ERT was also suggested to reduce the risk of cardiovascular disease in postmenopausal women, but the cardioprotective role of estrogen has been challenged after negative results in randomized trials. However, the mechanisms of estrogen action in atherosclerosis development are only partially known. In order to investigate the regulation of plasma low-density lipoprotein (LDL) cholesterol in postmenopausal women and the effects of ERT on cholesterol and glucose metabolism and blood pressure, 79 hysterectomized, non-diabetic postmenopausal women were randomized in a double-blind, double-dummy study to receive either peroral estradiol valerate (2 mg/day) or transdermal 17β-estradiol gel (1 mg estradiol/day) for six months. At baseline the level of LDL cholesterol was related to body mass index, the fractional catabolic rate (FCR) and the production of LDL apolipoprotein B (apo B), but not to cholesterol absorption efficiency. Both peroral and transdermal ERT decreased plasma total and LDL cholesterol, while high-density lipoprotein cholesterol and triglycerides increased only in the peroral group. The LDL-lowering response was related to changes in estrogen levels, which presumably enhance LDL receptor activity shown as an increase in FCR for LDL apo B. In contrast, the determined genetic factors, apo E phenotype, EcoRI and XbaI polymorphisms of the apo B gene and polymorphism of 7α-hydroxylase gene, were not significant in regulation of LDL cholesterol, neither did they modify the response of ERT in these postmenopausal women. Similar outcomes were observed with both peroral and transdermal ERT as regards glucose metabolism and blood pressure. The overall effect of ERT on glucose tolerance was found to be neutral. Blood pressure decreased among non-hypertensive subjects on both estrogens, which could be related, at least in part, to the alterations in vasoactive peptides. The data of the present study suggest an overall favorable effect of both peroral and transdermal estrogen on common cardiovascular risk factors. However, the clinical significance of these findings in the prevention of cardiovascular diseases needs to be proven in long-term, randomized trials.

No description available.

<p>It has been long known that many types of cancers have high metabolic requirements and use reprogrammed metabolism to support cellular activities. The first identified metabolic alteration in cancer cells was elevated glucose uptake, glycolysis activity and lactate production even in the presence of oxygen. This metabolic program, termed aerobic glycolysis or the Warburg effect, provides cells with energy as well as biosynthetic substrates to sustain cell survival and rapid cell proliferation. Cancer metabolism is closely linked to genetic mutations and oncogenic signaling pathways, such as PI3K/Akt, cMyc and HIF pathways. These oncogenic signals can direct metabolic reprogramming while changes in metabolic status can regulate activities of these signaling pathways in turn. In addition to glucose, later studies also found utilization of alternate nutrients in cancer cells, including glutamine and lipids. Glutamine is the second major metabolic fuel and can be converted to various substrates to support cell bioenergetics needs and biosynthetic reactions. Usage of metabolic fuels in cancer cells, however, is variable. While certain cancers display addiction to one type of nutrient, others are capable of using multiple nutrients. </p><p>The unique metabolic features of cancer cells raise the possibility of targeting metabolism as a novel therapeutic approach for cancer treatment. Using pharmacological inhibitors, previous research has provided corroborating evidence that metabolic stress can impact survival and growth of proliferative cancer cells by regulating cell apoptotic machinery and cell cycle checkpoints. Due to lack of genetic tools and side effects from these inhibitors, however, mechanistic understanding of cell response to metabolic inhibition was limited in these studies. More importantly, how metabolic stress affects cancer progression in a physiological condition has not yet been well investigated. Lastly, current research has not examined metabolic program in indolent cancers and the metabolic requirements and activities in less proliferative cells also remain to be understood.</p><p>This work examines nutrients utilization in B cell derived acute and chronic leukemia (B-ALL and B-CLL). B-ALL is an aggressive form of leukemia. Using cell lines and primary patient samples, we found B-ALL cells primarily used glucose through aerobic glycolysis, similar to other proliferative cancer cells. B-ALL cells were also more sensitive to inhibition of glycolysis than normal B cells. Employing an untargeted metabolomics profiling in combination with isotope labeled glucose tracing approach, we show in a B-ALL model that genetic ablation of glucose transporter Glut1 partially reduced glucose uptake, sufficiently hindered anabolic pathways and promoted catabolic metabolism. This metabolic shift led to sharply curtailed B-ALL proliferation in vitro and reduced leukemic burden in vivo. Furthermore, this partial inhibition of glucose metabolism sensitized B-ALL cells to apoptotic stimuli and non-cytotoxic metabolic inhibition significantly enhanced efficacy of a tyrosine kinase inhibitor to eliminate B-ALL cells in vitro and in vivo. Thus, partial inhibition of glucose metabolism can provide a plausible adjuvant therapy to treat cancers that depend on glycolysis for survival and proliferation. </p><p>In contrast to B-ALL, B-CLL is an indolent form of cancer. Most B-CLL cells exhibited low glucose metabolic activities that were comparable with normal B cells at resting stage. Similar to chronically stimulated and anergic B cells, these B-CLL cells also failed to upregulate glucose metabolism in response to IgM stimulation. We also observed an altered amino acid and acyl-carnitine profile and increased glutaminase mRNA in B-CLL relative to normal B cells, suggesting the capability of using alternate nutrients such as glutamine in these cells. Finally, we explored the possibility of suppressing mitochondria metabolism to induce B-CLL cell death through inhibition of the nuclear hormone receptor and metabolic regulator ERRalpha. ERRalpha is known to regulate mitochondrial metabolism and was expressed higher in B-CLL than normal B cells. ERRalpha inhibition decreased viability of oncogene transformed pro-B cells, suggesting ERRalpha as a potential target for B-CLL treatment.</p><p> Collectively, this work investigates metabolic phenotype in two forms of leukemia derived from B cells. It reveals different metabolic requirements and activities in aggressive and indolent leukemia and explores different approaches to suppress metabolism in these cancers. Findings of this work shed light on how to potentially design metabolic approach to improve cancer treatment.</p> / Dissertation

A oligopeptidase neurolina (E.C.3.4.24.16; nln ) foi identificado pela primeira vez em membranas sinápticas de cérebro de ratos como sendo capaz de participar no metabolismo de peptídeos bioativos, como neurotensina e bradicinina. Recentemente, foi sugerido que a ausência de Nln pode melhorar a sensibilidade a insulina. Aqui, nós mostrado que camundongos knockout para Nln (KO) são mais tolrerantes à glicose, sensíveis à insulina e apresentam maior gliconeogênese. Os animais KO apresentou um aumento na expressão de mRNA de vários genes relacionados com a gliconeogênese no fígado. A semiquantificação de peptídeos intracelulares revelou um aumento em peptídeos intracelulares específicos no gastrocnêmio e tecido adiposo epididimal, que estão envolvidos com o aumento da tolerância a glicose e maior sensibilidade à insulina nos animais KO. Esses resultados sugerem fortemente a nova possibilidade de que Nln é uma enzima chave no metabolismo energético e pode ser um novo alvo terapêutico para melhorar a captação de glicose e sensibilidade a insulina. / The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln knockout mice (KO) have increased glucose tolerance, insulin sensitivity and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semi-quantitative peptidomic analysis suggests increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity.

京都大学 / 0048 / 新制・課程博士 / 博士(人間・環境学) / 甲第22533号 / 人博第936号 / 新制||人||223(附属図書館) / 2019||人博||936(吉田南総合図書館) / 京都大学大学院人間・環境学研究科共生人間学専攻 / (主査)教授 林 達也, 教授 石原 昭彦, 教授 久代 恵介 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DGAM

Jean Mayer has postulated the presence of glucoreceptors located primarily in the ventromedial hypothalamic nuclei of the brain which are activated by glucose in the measure that they utilize it. According to Mayer, hunger occurs when glucose is not available for metabolic purposes and satiation supervenes when glucose is made available. Control of this mechanism rests with the glucoreceptors. These receptors are believed to be destroyed when an injection of the compound goldthioglucose is given to mice. These animals subsequently become obese and are found to have gold deposits and lesions in the ventromedial area and also in other parts of the brain. If the glucoreceptors are destroyed and cannot respond to the presence of glucose in the blood, it would be predicted that food intake would not change with the glucose level. The purpose of this investigation was to see if the food intake of goldthioglucose injected animals is affected by a glucose injection. One hundred and twenty mice were divided into four groups. One group, the controls, received no goldthioglucose. The other three groups received the following dosages: .5 mg. of goldthioglucose per gram of body weight, 1.0 mg. of goldthioglucose per gram of body weight and 1.3 mg. of goldthioglucose per gram of body weight. Fifty seven days after the goldthioglucose injection a training period began in which the mice were taught to consume their entire daily food intake during a 50 minute period. Then the experimental period began during which the animals were maintained on the 23 hour and 10 minute deprivation schedule. During this period the mice were given intraperitoneal injections of 60 mg. of glucose or normal saline on alternate days for ten days. The amount of food consumed in the 50 minutes beginning 15 minutes after the glucose or saline injection was determined. Food intake of the goldthioglucose injected animals was not different than that of the controls under any factor of the experiment. The results do not support Mayer's idea that the glucoreceptors as he describes them are destroyed by goldthioglucose.

Aging of the hematopoietic system promotes various immune and systemic disorders and is driven in-part by dysfunction of life-long self-renewing hematopoietic stem cells (HSC). Autophagy is required for the benefit associated with activation of conserved longevity signaling programs and is essential for HSC function in response to various stressors. With age, some HSCs basally increase autophagy flux and maintain inert metabolic activity. This autophagy-activated subset is responsible for the residual regenerative capacity of old stem cells, but the mechanisms promoting autophagy activation in HSC aging remain unknown. Here, we demonstrate that autophagy is a response to chronic inflammation in the aging HSC niche. Chronic inflammation impairs glucose metabolism in young and old HSCs (oHSC) by impeding AKT-FOXO intracellular signaling networks. We find that autophagy enables metabolic adaptation of oHSCs to non-glucose energy substrates for functional maintenance. Notably, water-only fasting transiently further activates autophagy in oHSCs, and upon refeeding normalizes glucose uptake and glycolytic flux as well as regenerative output. Our results demonstrate that inflammation-driven glucose hypometabolism impairs oHSC regenerative capacity, that autophagy activation metabolically adapts oHSCs to an inflamed niche, and that autophagy is a modulable node to restore glycolytic and regenerative capacity during stem cell aging.