Blanca Gavilán-Carrera , Vivianna Aguilera-Fernández , Francisco J. Amaro-Gahete , Antonio Rosales-Castillo , Alberto Soriano-Maldonado , José Antonio Vargas-Hitos
{"title":"Association of the Mediterranean diet with arterial stiffness, inflammation, and medication use in women with systemic lupus erythematosus: An exploratory study","authors":"Blanca Gavilán-Carrera , Vivianna Aguilera-Fernández , Francisco J. Amaro-Gahete , Antonio Rosales-Castillo , Alberto Soriano-Maldonado , José Antonio Vargas-Hitos","doi":"10.1016/j.jnutbio.2024.109759","DOIUrl":"10.1016/j.jnutbio.2024.109759","url":null,"abstract":"<div><div>Patients with systemic lupus erythematosus (SLE) face increased cardiovascular risk not fully explained by traditional cardiovascular risk factors. Arterial stiffness, inflammation and disease-related therapies may be contributors to augmented cardiovascular risk, whereas healthy dietary habits could help in their management. The aim of the present study was to analyze the association of the adherence to the Mediterranean Diet with arterial stiffness, inflammation, and disease-related medication in women with SLE. A total of 76 women with SLE were included in this cross-sectional exploratory study. The adherence to the Mediterranean Diet was assessed using the Mediterranean Diet Score. Arterial stiffness was measured through pulse wave velocity (PWV). Inflammatory profile was evaluated through high-sensitivity C-reactive protein (hsCRP). The use (yes / no) and doses (mg /day and cumulative dose over the last 3 years) of corticosteroids and immunosuppressants were also registered. No association of the overall adherence to the Mediterranean Diet with PWV, hsCRP or medication use was found (all <em>P</em>>.05). Lower intake of full dairy products was related to greater odds of corticosteroids use (odds=1.72; <em>P</em>=.004), and both higher current (β=0.29; <em>P</em>=.024) and cumulative (β=0.21; <em>P</em>=.040) doses. Lower intake of red wine was associated with lower odds of immunosuppressants use (odds=0.63; <em>P</em>=.008). No association of the adherence to the Mediterranean Diet with arterial stiffness, inflammation or disease-related medication was observed in women with SLE with mild disease activity. However, higher dairy products and lower red wine consumption were related to lower use of disease-related medication. Future intervention studies are needed to better understand how nutritional education promoting Mediterranean Diet food groups can complement conventional SLE treatments.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109759"},"PeriodicalIF":4.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qingqing Zhu , Xinyi Lu , Ting Zhang , Mengsha Shi , Rongrong Gao , Yanli Zhou , Haifeng Zhang , Wenming Yao , Changyong Qi , Shengen Liao , Xinli Li
{"title":"Resistant starch confers protection of dietary against diabetic cardiomyopathy","authors":"Qingqing Zhu , Xinyi Lu , Ting Zhang , Mengsha Shi , Rongrong Gao , Yanli Zhou , Haifeng Zhang , Wenming Yao , Changyong Qi , Shengen Liao , Xinli Li","doi":"10.1016/j.jnutbio.2024.109766","DOIUrl":"10.1016/j.jnutbio.2024.109766","url":null,"abstract":"<div><div>Long-term dysfunction of glucose metabolism causes cardiac dysfunction called diabetic cardiomyopathy (DCM). To investigate the effect and underlying mechanism of RS on the process of DCM, mouse models induced by a high-fat diet (HFD) and streptozotocin (STZ) were fed RS (2 g/kg/day) and vehicle treatment (by oral gavage) for 14 weeks. Various analyses, including qRT-PCR, western blot, immunofluorescence staining, histology staining, cardiac function, and diversity detection of intestinal microbiota were performed. RS intervention could directly improve myocardial fibrosis, hypertrophy, apoptosis, and cardiac insufficiency in DCM. These beneficial effects may be achieved by elevating the expression of IGF-1, activating the ERK phosphorylation. Furthermore, by carrying out nano LC-MS/MS analyses and 16S rDNA sequencing, we found RS might primarily affect proteins in the cytoplasm involved in post-translational modification, protein conversion, and signal transduction mechanisms. RS altered intestinal microbiota and improved intestinal mucosal permeability towards a favorable direction in DCM. This multidimensional assessment of RS suggests that might be a promising approach towards the treatment of DCM.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109766"},"PeriodicalIF":4.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mi-Jeong Kim , Taeyeon Hwang , Sugyeong Ha , Hyerin Kim , Jeongwon Kim , Doyeon Kim , Ji-an Yoo , Byeong Moo Kim , Hae Young Chung , Donghwan Kim , Jaewon Lee , Haeseung Lee , Sangok Kim , Ki Wung Chung
{"title":"Calorie restriction exacerbates folic acid-induced kidney fibrosis by altering mitochondria metabolism","authors":"Mi-Jeong Kim , Taeyeon Hwang , Sugyeong Ha , Hyerin Kim , Jeongwon Kim , Doyeon Kim , Ji-an Yoo , Byeong Moo Kim , Hae Young Chung , Donghwan Kim , Jaewon Lee , Haeseung Lee , Sangok Kim , Ki Wung Chung","doi":"10.1016/j.jnutbio.2024.109765","DOIUrl":"10.1016/j.jnutbio.2024.109765","url":null,"abstract":"<div><div>Calorie restriction (CR) is known to confer health benefits, including longevity and disease prevention. Although CR is promising in preventing chronic kidney disease (CKD), its potential impact on the progression of kidney fibrosis from acute kidney injury (AKI) to CKD remains unclear. Here, we present evidence that CR exacerbates renal damage in a mouse model of folic acid (FA)-induced renal fibrosis by altering mitochondrial metabolism and inflammation. Mice subjected to CR (60% of <em>ad libitum</em>) for three days were subjected to high dose of FA (250 mg/kg) injection and maintained under CR for an additional week before being sacrificed. Biochemical analyses showed that CR mice exhibited increased kidney injury and fibrosis. RNA sequencing analysis demonstrated decreased electron transport and oxidative phosphorylation (OXPHOS) in CR kidneys with injury, heightened inflammatory, and fibrotic responses. CR significantly decreased <em>OXPHOS</em> gene and protein levels and reduced β-oxidation-associated proteins in the kidney. To determine whether defects in mitochondrial metabolism is associated with inflammation in the kidney, further <em>in vitro</em> experiments were performed. NRK52E kidney epithelial cells were treated with antimycin A to induce mitochondrial damage. Antimycin A treatment significantly increased chemokine expression via a STING-dependent pathway. Serum restriction in NRK49F kidney fibroblasts was observed to enhance the fibrotic response induced by TGFβ under in vitro conditions. In summary, our results indicate that CR exacerbates fibrosis and inflammatory responses in the kidney by altering mitochondrial metabolism, highlighting the importance of adequate energy supply for an effective response to AKI and fibrosis development.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109765"},"PeriodicalIF":4.8,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glucosamine inhibits myoblast proliferation and differentiation, and stimulates myotube atrophy through distinct signal pathways","authors":"Shui-Yu Liu , Luen-Kui Chen , Yi-Ting Chung , Chien-Wei Chen , Guan-Lin Wu , Yi-Chieh Chang , Pin-Rong Chen , Yuan-I Chang , Heng-Fu Lin , Liang-Yi Wu , Chi-Chang Juan","doi":"10.1016/j.jnutbio.2024.109762","DOIUrl":"10.1016/j.jnutbio.2024.109762","url":null,"abstract":"<div><div>Glucosamine (GlcN) is one of the dietary supplements used in the treatment of osteoarthritis. Endogenously, GlcN is synthesized from glucose through the hexosamine pathway. In addition to ameliorating arthritis, several biological functions of GlcN have been reported, including insulin resistance in skeletal muscle. However, the regulatory role of GlcN in skeletal muscle development is not clear. We therefore investigated the effect of GlcN on myoblast proliferation, differentiation, and myotube development and their underlying mechanisms in C2C12 cells. Myoblast proliferation was measured by MTT assay. The expressions of MyoD, myogenin (MyoG), and myosin heavy chain (MyHC) were identified as determinants of myoblast differentiation. Expressions of atrogin-1 and muscle RING-finger protein-1 (MuRF-1) were identified as markers of myotube atrophy. The results show that treatment with GlcN significantly reduced myoblast proliferation and phosphorylation of Stat3 and S6K. These findings suggest that GlcN can inhibit growth of myoblasts through inhibiting phosphorylation of Stat3 and S6K. In addition, GlcN significantly suppressed the expression of MyoD, MyoG, and MyHC, as well as myotube formation. Pretreatment of C2C12 myoblast cells with ER stress inhibitors significantly blocked GlcN-inhibited MyHC expression and myotube formation. It can be concluded that GlcN suppressed myogenic differentiation via a pathway that involved ER stress. Moreover, GlcN decreased myotube diameter and expression of MyHC, as well as increased MuRF-1 in C2C12 myotubes. Meanwhile, GlcN also reduced the expressions of phosphorylated Akt and mTOR were stimulated after GlcN treatment in C2C12 myotubes. Thus, GlcN induced skeletal muscle atrophy by inhibiting the protein synthesis pathway. Chronic GlcN infusion also caused skeletal muscle atrophy in mice. In conclusion, GlcN regulated important stages of skeletal muscle development through different signaling pathways.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109762"},"PeriodicalIF":4.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Margaret J. Morris , Kyoko Hasebe , Arya L. Shinde , Michael K. H Leong , Md. Mustahsan Billah , Sonia Hesam-Shariati , Michael D. Kendig
{"title":"Time-restricted feeding does not prevent adverse effects of palatable cafeteria diet on adiposity, cognition and gut microbiota in rats","authors":"Margaret J. Morris , Kyoko Hasebe , Arya L. Shinde , Michael K. H Leong , Md. Mustahsan Billah , Sonia Hesam-Shariati , Michael D. Kendig","doi":"10.1016/j.jnutbio.2024.109761","DOIUrl":"10.1016/j.jnutbio.2024.109761","url":null,"abstract":"<div><div>Time-restricted feeding (TRF) is a popular dietary strategy whereby daily food intake is limited to a <12h window. As little is known about the effects of TRF on cognitive and behavioral measures, the present study examined the effects of time-restricted (8h/day; zeitgeber time [ZT]12–20) or continuous access to a high-fat, high-sugar cafeteria-style diet (Caf; Caf and Caf-TRF groups; <em>n</em>=12 adult male Sprague-Dawley rats) or standard chow (Chow and Chow-TRF groups) on short-term memory, anxiety-like behavior, adiposity and gut microbiota composition over 13-weeks with daily food intake measures. TRF significantly reduced daily energy intake in Caf- but not chow-fed groups. In Caf-fed groups, TRF reduced the proportion of energy derived from sugar while increasing that derived from protein. Caf diet significantly increased weight gain, adiposity and fasting glucose within 4 weeks; TRF partially reduced these effects. Caf diet increased anxiety-like behavior in the Elevated Plus Maze in week 3 but not week 12, and impaired hippocampal-dependent place recognition memory in week 11; neither measure was affected by TRF. Global microbiota composition differed markedly between chow and Caf groups, with a small effect of TRF in rats fed chow. In both chow and Caf diet groups, TRF reduced microbiota alpha diversity measures of Shannon diversity and evenness relative to continuous access. Results indicate only limited benefits of TRF access to an obesogenic diet under these conditions, suggesting that more severe time restriction may be required to offset adverse metabolic and cognitive effects when using highly palatable diets.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109761"},"PeriodicalIF":4.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Azhar S. Sindi , Lisa F. Stinson , Ching Tat Lai , Zoya Gridneva , Gabriela E. Leghi , Merryn J. Netting , Mary E. Wlodek , Beverly S. Muhlhausler , Xiaojie Zhou , Matthew S. Payne , Donna T. Geddes
{"title":"Human milk lactoferrin and lysozyme concentrations vary in response to a dietary intervention","authors":"Azhar S. Sindi , Lisa F. Stinson , Ching Tat Lai , Zoya Gridneva , Gabriela E. Leghi , Merryn J. Netting , Mary E. Wlodek , Beverly S. Muhlhausler , Xiaojie Zhou , Matthew S. Payne , Donna T. Geddes","doi":"10.1016/j.jnutbio.2024.109760","DOIUrl":"10.1016/j.jnutbio.2024.109760","url":null,"abstract":"<div><div>It is known that human milk (HM)<span><span><sup>1</sup></span></span> antimicrobial protein composition varies during lactation. However, the impact of maternal diet on these antimicrobial proteins, particularly lactoferrin and lysozyme remains unknown. In addition, it is unclear whether daily, circadian, and between breast variations exist for lactoferrin and lysozyme concentrations. We investigated the impact of a low sugar, low fat, high fibre dietary intervention on HM lysozyme and lactoferrin concentrations. HM was sampled across a 3-week period; daily, at different times of day, and from both breasts to measure the level of intraindividual variation. The intervention significantly reduced maternal sugar, total fat, and saturated fat intake. HM lactoferrin concentration declined significantly over the course of the intervention however the effect size was relatively small. In addition, lactoferrin and lysozyme concentrations were variable over time, and differed significantly within and across the day but not between breasts.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109760"},"PeriodicalIF":4.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruce A. Watkins , Jeremy R. Watkins , Robert B. Rucker
{"title":"Commentary—research diets and reproducible results in rodent models","authors":"Bruce A. Watkins , Jeremy R. Watkins , Robert B. Rucker","doi":"10.1016/j.jnutbio.2024.109750","DOIUrl":"10.1016/j.jnutbio.2024.109750","url":null,"abstract":"","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109750"},"PeriodicalIF":4.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coconut oil affects aging-related changes in Mongolian gerbil liver morphophysiology","authors":"Vitor Grigio , Luiz Henrique Alves Guerra , Stella Bicalho Silva , Mariella Bontempo Freitas , Sebastião Roberto Taboga , Patrícia Simone Leite Vilamaior","doi":"10.1016/j.jnutbio.2024.109749","DOIUrl":"10.1016/j.jnutbio.2024.109749","url":null,"abstract":"<div><div>Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109749"},"PeriodicalIF":4.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivo Vieira de Sousa Neto , Ana Paula Pinto , Rosangela Vieira de Andrade , Fabiane Hiratsuka Veiga de Souza , Paulo Eduardo Narcizo de Souza , Victória Assis , Ramires Alsamir Tibana , Rodrigo Vanerson Passos Neves , Thiago Santos Rosa , Jonato Prestes , Adelino Sanchez Ramos da Silva , Rita de Cassia Marqueti
{"title":"Paternal exercise induces antioxidant defenses by α-Klotho/Keap1 pathways in the skeletal muscle of offspring exposed to a high fat-diet without changing telomere length","authors":"Ivo Vieira de Sousa Neto , Ana Paula Pinto , Rosangela Vieira de Andrade , Fabiane Hiratsuka Veiga de Souza , Paulo Eduardo Narcizo de Souza , Victória Assis , Ramires Alsamir Tibana , Rodrigo Vanerson Passos Neves , Thiago Santos Rosa , Jonato Prestes , Adelino Sanchez Ramos da Silva , Rita de Cassia Marqueti","doi":"10.1016/j.jnutbio.2024.109747","DOIUrl":"10.1016/j.jnutbio.2024.109747","url":null,"abstract":"<div><div>Although previous studies demonstrated that the ancestral lifestyle can enhance the metabolic health of offspring exposed to an obesogenic diet, the specific connections between these positive effects in redox state and telomere length are unknown. We investigated the impact of paternal resistance training (RT) on stress-responsive signaling and the pathways involved in telomere homeostasis in skeletal muscle. This investigation encompassed both the fathers and first-generation litter exposed to a long-term standard diet (24 weeks) and high fat diet (HFD). Wistar rats were randomized into sedentary or trained fathers (8 weeks of resistance training). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups: offspring of sedentary or trained fathers exposed to either a control diet or HFD. The gastrocnemius was prepared for reverse transcription-quantitative polymerase chain reaction, immunoblotting, ELISA, and electron paramagnetic resonance spectroscopy. RT upregulated shelterin mRNA levels and antioxidant protein, preserving muscle telomere in fathers. Conversely, HFD induced a disturbance in the redox balance, which may have contributed to the offspring telomere shortening from sedentary fathers. Preconceptional paternal RT downregulates Kelch-like ECH-associated protein 1 (<em>Keap1)</em> mRNA levels in the skeletal muscle of progeny exposed to HFD, driving an increase in Glutathione reductase mRNA levels, Sod1 and Catalase protein levels to mitigate ROS production. Also, paternal exercise upregulates α-Klotho protein levels, mediating antioxidative responses without altering shelterin mRNA levels and telomere length. We provide the first in-depth analysis that the offspring's redox state seems to be directly associated with the beneficial effects of paternal exercise.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109747"},"PeriodicalIF":4.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shichao Xiong, Qingxia Wang, Yiru Chen, Huidi Du, Yan Zhao
{"title":"Leptin limits hepatic lipid accumulation and inflammation via vagal activation of the JAK2-STAT3/AMPK pathway","authors":"Shichao Xiong, Qingxia Wang, Yiru Chen, Huidi Du, Yan Zhao","doi":"10.1016/j.jnutbio.2024.109748","DOIUrl":"10.1016/j.jnutbio.2024.109748","url":null,"abstract":"<div><div>Non-Alcoholic Fatty Liver Disease (NAFLD) begins with hepatic lipid accumulation, and leptin has antisteatosis properties. In this study, we investigated the effects of leptin on hepatic steatosis and inflammation through the vagal pathway independently of the inhibitory effect of food intake. Male Sprague-Dawley rats were matched for food intake after the high-fat diet (HFD)-induced obesity model and were injected intraperitoneally with leptin or leptin + lidocaine for 6 weeks. Control rats received equal volumes of saline. Adipose tissue mass, NAFLD activity scores (NAS), hepatic inflammatory factors, hepatic triglyceride content and hepatic lipid metabolism-related protein levels were evaluated. Leptin ameliorated HFD-induced hepatic lipid accumulation, improved NAS, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) levels in the presence of matched intake. Lidocaine decreased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) expression in the nucleus tractus solitarius (NTS) and abrogated the leptin-mediated improvement. Leptin increased hypothalamic phosphorylated Janus kinase 2 (p-JAK2) and p-STAT3 expression, as well as the expression of mitochondrial respiratory chain-related genes. Leptin also increased hepatic phosphorylated adenosine 5′-monophosphate-activated protein kinase (p-AMPK) expression and phosphorylation of its downstream target acetyl Co A carboxylase 1 (ACC1), reducing de novo lipogenesis. Our results suggest that leptin ameliorated hepatic lipid accumulation and inflammation by activating the JAK2-STAT3/AMPK pathway through the vagal pathway independently of the inhibitory effect of ingestion. Leptin has the potential to be a drug for early NAFLD treatment.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109748"},"PeriodicalIF":4.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}