bims-obesme 2024-04-14 papers

bims-obesme

Biomed News

on Obesity metabolism

Issue of 2024–04–14
twelve papers selected by
Xiong Weng, University of Edinburgh

Adipose tissue macrophages secrete small extracellular vesicles that mediate rosiglitazone-induced insulin sensitization.
Role of liver FGF21-KLB signaling in ketogenic diet-induced amelioration of hepatic steatosis.
Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise.
Deciphering the molecular pathways of saroglitazar: A dual PPAR α/γ agonist for managing metabolic NAFLD.
Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance.
Glucose regulation of adipose tissue browning by CBP/p300- and HDAC3-mediated reversible acetylation of CREBZF.
Ironing out obesity.
Interleukin-6 promotes visceral adipose tissue accumulation during aging via inhibiting fat lipolysis.
Krüppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4α-mediated metabolic pathways.
Irisin influences the in vitro differentiation of human mesenchymal stromal cells, promoting a tendency toward beiging adipogenesis.
Insulin regulation of regional lipolysis in upper-body obese and lean humans.
A novel fatty acid analogue triggers CD36-GPR120 interaction and exerts anti-inflammatory action in endotoxemia.

Nat Metab. 2024 Apr 11.

Adipose tissue macrophages secrete small extracellular vesicles that mediate rosiglitazone-induced insulin sensitization.

Theresa V Rohm, Felipe Castellani Gomes Dos Reis, Roi Isaac, Cairo Murphy, Karina Cunha E Rocha, Gautam Bandyopadhyay, Hong Gao, Avraham M Libster, Rizaldy C Zapata, Yun Sok Lee, Wei Ying, Charlene Miciano, Allen Wang, Jerrold M Olefsky.

The obesity epidemic continues to worsen worldwide, driving metabolic and chronic inflammatory diseases. Thiazolidinediones, such as rosiglitazone (Rosi), are PPARγ agonists that promote 'M2-like' adipose tissue macrophage (ATM) polarization and cause insulin sensitization. As ATM-derived small extracellular vesicles (ATM-sEVs) from lean mice are known to increase insulin sensitivity, we assessed the metabolic effects of ATM-sEVs from Rosi-treated obese male mice (Rosi-ATM-sEVs). Here we show that Rosi leads to improved glucose and insulin tolerance, transcriptional repolarization of ATMs and increased sEV secretion. Administration of Rosi-ATM-sEVs rescues obesity-induced glucose intolerance and insulin sensitivity in vivo without the known thiazolidinedione-induced adverse effects of weight gain or haemodilution. Rosi-ATM-sEVs directly increase insulin sensitivity in adipocytes, myotubes and primary mouse and human hepatocytes. Additionally, we demonstrate that the miRNAs within Rosi-ATM-sEVs, primarily miR-690, are responsible for these beneficial metabolic effects. Thus, using ATM-sEVs with specific miRNAs may provide a therapeutic path to induce insulin sensitization.

DOI: https://doi.org/10.1038/s42255-024-01023-w
Nutr Diabetes. 2024 Apr 12. 14(1): 18

Role of liver FGF21-KLB signaling in ketogenic diet-induced amelioration of hepatic steatosis.

Wanrong Guo, Huanyi Cao, Yunfeng Shen, Wuguo Li, Wei Wang, Lidan Cheng, Mengyin Cai, Fen Xu.

BACKGROUND: The effectiveness of ketogenic diet (KD) in ameliorating fatty liver has been established, although its mechanism is under investigation. Fibroblast growth factor 21 (FGF21) positively regulates obesity-associated metabolic disorders and is elevated by KD. FGF21 conventionally initiates its intracellular signaling via receptor β-klotho (KLB). However, the mechanistic role of FGF21-KLB signaling for KD-ameliorated fatty liver remains unknown. This study aimed to delineate the critical role of FGF21 signaling in the ameliorative effects of KD on hepatic steatosis.
METHODS: Eight-week-old C57BL/6 J mice were fed a chow diet (CD), a high-fat diet (HFD), or a KD for 16 weeks. Adeno-associated virus-mediated liver-specific KLB knockdown mice and control mice were fed a KD for 16 weeks. Phenotypic assessments were conducted during and after the intervention. We investigated the mechanism underlying KD-alleviated hepatic steatosis using multi-omics and validated the expression of key genes.
RESULTS: KD improved hepatic steatosis by upregulating fatty acid oxidation and downregulating lipogenesis. Transcriptional analysis revealed that KD dramatically activated FGF21 pathway, including KLB and fibroblast growth factor receptor 1 (FGFR1). Impairing liver FGF21 signaling via KLB knockdown diminished the beneficial effects of KD on ameliorating fatty liver, insulin resistance, and regulating lipid metabolism.
CONCLUSION: KD demonstrates beneficial effects on diet-induced metabolic disorders, particularly on hepatic steatosis. Liver FGF21-KLB signaling plays a critical role in the KD-induced amelioration of hepatic steatosis.

DOI: https://doi.org/10.1038/s41387-024-00277-3
Molecules. 2024 Mar 27. pii: 1494. [Epub ahead of print]29(7):

Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise.

Thomai Mouskeftara, Olga Deda, Grigorios Papadopoulos, Antonios Chatzigeorgiou, Helen Gika.

  Detailed investigation of the lipidome remodeling upon normal weight conditions, obesity, or weight loss, as well as the influence of physical activity, can help to understand the mechanisms underlying dyslipidemia in metabolic conditions correlated to the emergence and progression of non-alcoholic fatty liver disease (NAFLD). C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 20 weeks. Subgroups within the high-fat diet (HFD) group underwent different interventions: some engaged in exercise (HFDex), others were subjected to weight loss (WL) by changing from the HFD to ND, and some underwent a combination of weight loss and exercise (WLex) during the final 8 weeks of the 20-week feeding period. To support our understanding, not only tissue-specific lipid remodeling mechanisms but also the cross-talk between different tissues and their impact on the systemic regulation of lipid metabolism are essential. Exercise and weight loss-induced specific adaptations in the liver and visceral adipose tissue lipidomes of mice were explored by the UPLC-TOF-MS/MS untargeted lipidomics methodology. Lipidomic signatures of ND and HFD-fed mice undergoing weight loss were compared with animals with and without physical exercise. Several lipid classes were identified as contributing factors in the discrimination of the groups by multivariate analysis models, such as glycerolipids, glycerophospholipids, sphingolipids, and fatty acids, with respect to liver samples, whereas triglycerides were the only lipid class identified in visceral adipose tissue. Lipids found to be dysregulated in HFD animals are related to well-established pathways involved in the biosynthesis of PC, PE, and TG metabolism. These show a reversing trend back to basic levels of ND when animals change to a normal diet after 12 weeks, whereas the impact of exercise, though in some cases it slightly enhances the reversing trend, is not clear.

Keywords:  adipose tissue; de novo lipogenesis; exercise; lipidomics; liver; non-alcoholic fatty liver disease

DOI:  https://doi.org/10.3390/molecules29071494
Metabolism. 2024 Apr 10. pii: S0026-0495(24)00138-0. [Epub ahead of print] 155912

Deciphering the molecular pathways of saroglitazar: A dual PPAR α/γ agonist for managing metabolic NAFLD.

Devaraj Ezhilarasan.

  Saroglitazar (SARO), a dual peroxisome proliferator activated receptor (PPAR)-α/γ agonist, has been used to treat metabolic diseases such as insulin resistance and diabetic dyslipidemia in patients with non-alcoholic fatty liver disease (NAFLD). SARO, administered at a dose of 4 mg/day, has been consistently studied in clinical trials with different time points ranging from 4 to 24 weeks with NAFLD patients. Due to its PPAR-γ agonistic action, SARO prevents adipose tissue-mediated fatty acid delivery to the liver by increasing insulin sensitivity and regulating adiponectin and leptin levels in adipose tissue. In hepatocytes, SARO induces fatty acid β-oxidation in mitochondria and transcriptionally activates lipid metabolizing genes in peroxisomes. SARO inhibits insulin resistance, thereby preventing the activation of sterol regulatory element-binding proteins -1c and carbohydrate response element binding protein in hepatocytes through its PPAR-α agonistic action. SARO treatment reduces lipotoxicity-mediated oxidative stress by activating the nuclear factor erythroid 2-related factor 2 and transcriptionally expressing the antioxidants from the antioxidant response element in the nucleus through its PPAR-γ agonistic action. SARO provides a PPAR-α/γ-mediated anti-inflammatory effect by preventing the phosphorylation of mitogen-activated protein kinases (JNK and ERK) and nuclear factor kappa B in hepatocytes. Additionally, SARO interferes with transforming growth factor-β/Smad downstream signaling, thereby reducing liver fibrosis progression through its PPAR-α/γ agonistic actions. Thus, SARO improves insulin resistance and dyslipidemia in NAFLD, reduces lipid accumulation in the liver, and thereby prevents mitochondrial toxicity, oxidative stress, inflammation, and fibrosis progression. This review summarizes the possible molecular mechanism of SARO in the NAFLD.

Keywords:  Chronic liver diseases; Fatty liver; High fat diet; Liver steatosis; Oxidative stress

DOI:  https://doi.org/10.1016/j.metabol.2024.155912
JCI Insight. 2024 Apr 08. pii: e174164. [Epub ahead of print]9(7):

Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance.

Nadejda Bozadjieva-Kramer, Jae Hoon Shin, Ziru Li, Alan C Rupp, Nicole Miller, Stace Kernodle, Nicolas Lanthier, Paulina Henry, Nikhil Seshadri, Andriy Myronovych, Ormond A MacDougald, Robert W O'Rourke, Rohit Kohli, Charles F Burant, Amy E Rothberg, Randy J Seeley.

  Fibroblast growth factor 15/19 (FGF15/19, mouse/human ortholog) is expressed in the ileal enterocytes of the small intestine and released postprandially in response to bile acid absorption. Previous reports of FGF15-/- mice have limited our understanding of gut-specific FGF15's role in metabolism. Therefore, we studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol, glucose, and energy balance. We found that circulating levels of FGF19 were reduced in individuals with obesity and comorbidities, such as type 2 diabetes and metabolic dysfunction-associated fatty liver disease. Gene expression analysis of ileal FGF15-positive cells revealed differential expression during the obesogenic state. We fed standard chow or a high-fat metabolic dysfunction-associated steatohepatitis-inducing diet to control and intestine-derived FGF15-knockout (FGF15INT-KO) mice. Control and FGF15INT-KO mice gained similar body weight and adiposity and did not show genotype-specific differences in glucose, mixed meal, pyruvate, and glycerol tolerance. FGF15INT-KO mice had increased systemic bile acid levels but decreased cholesterol levels, pointing to a primary role for gut-derived FGF15 in regulating bile acid and cholesterol metabolism when exposed to obesogenic diet. These studies show that intestinal FGF15 plays a specific role in bile acid and cholesterol metabolism regulation but is not essential for energy and glucose balance.

Keywords:  Cholesterol; Gastroenterology; Glucose metabolism; Metabolism; Obesity

DOI:  https://doi.org/10.1172/jci.insight.174164
Proc Natl Acad Sci U S A. 2024 Apr 16. 121(16): e2318935121

Glucose regulation of adipose tissue browning by CBP/p300- and HDAC3-mediated reversible acetylation of CREBZF.

Aoyuan Cui, Yaqian Xue, Weitong Su, Jing Lin, Yuxiao Liu, Genxiang Cai, Qin Wan, Yang Jiang, Dong Ding, Zengpeng Zheng, Shuang Wei, Wenjing Li, Jiaxin Shen, Jian Wen, Mengyao Huang, Jiuxiang Zhao, Xiaojie Zhang, Yuwu Zhao, Hong Li, Hao Ying, Haibing Zhang, Yan Bi, Yan Chen, Aimin Xu, Yong Xu, Yu Li.

  Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.

Keywords:  CREBZF; adipose tissue; glucose-sensing pathway; reversible acetylation; thermogenesis

DOI:  https://doi.org/10.1073/pnas.2318935121
Trends Endocrinol Metab. 2024 Apr 09. pii: S1043-2760(24)00084-5. [Epub ahead of print]

Ironing out obesity.

Gabriel O de Souza, Willian O Dos Santos, Jose Donato.

  Obesity is associated with dysfunctions in hypothalamic neurons that regulate metabolism, including agouti-related protein (AgRP)-expressing neurons. In a recent article, Zhang et al. demonstrated that either diet- or genetically induced obesity promoted iron accumulation specifically in AgRP neurons. Preventing iron overload in AgRP neurons mitigated diet-induced obesity and related comorbidities in male mice.

Keywords:  hypothalamus; insulin resistance; iron; leptin resistance; obesity

DOI:  https://doi.org/10.1016/j.tem.2024.04.001
Int Immunopharmacol. 2024 Apr 08. pii: S1567-5769(24)00424-7. [Epub ahead of print]132 111906

Interleukin-6 promotes visceral adipose tissue accumulation during aging via inhibiting fat lipolysis.

Xiaofang Zhang, Qingxuan Wang, Yaru Wang, Chen Ma, Qing Zhao, Hongyan Yin, Long Li, Dongmei Wang, Yinxiang Huang, Yan Zhao, Xiulin Shi, Xuejun Li, Caoxin Huang.

   BACKGROUND: Age-related visceral obesity could contribute to the development of cardiometabolic complications. The pathogenesis of visceral fat mass accumulation during the aging process remains complex and largely unknown. Interleukin-6 (IL-6) has emerged as one of the prominent inflammaging markers which are elevated in circulation during aging. However, the precise role of IL-6 in regulating age-related visceral adipose tissue accumulation remains uncertain.
RESULTS: A cross-sectional study including 77 older adults (≥65 years of age) was initially conducted. There was a significant positive association between serum IL-6 levels and visceral fat mass. We subsequently validated a modest but significant elevation in serum IL-6 levels in aged mice. Furthermore, we demonstrated that compared to wildtype control, IL-6 deficiency (IL-6 KO) significantly attenuated the accumulation of visceral adipose tissue during aging. Further metabolic characterization suggested that IL-6 deficiency resulted in improved lipid metabolism parameters and energy expenditure in aged mice. Moreover, histological examinations of adipose depots revealed that the absence of IL-6 ameliorated adipocyte hypertrophy in visceral adipose tissue of aged mice. Mechanically, the ablation of IL-6 could promote the PKA-mediated lipolysis and consequently mitigate lipid accumulation in adipose tissue in aged mice.
CONCLUSION: Our findings identify a detrimental role of IL-6 during the aging process by promoting visceral adipose tissue accumulation through inhibition of lipolysis. Therefore, strategies aimed at preventing or reducing IL-6 levels may potentially ameliorate age-related obesity and improve metabolism during aging.

Keywords:  Aging; IL-6; Lipolysis; Obesity; Visceral adipose

DOI:  https://doi.org/10.1016/j.intimp.2024.111906
Metabolism. 2024 Apr 04. pii: S0026-0495(24)00135-5. [Epub ahead of print]155 155909

Krüppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4α-mediated metabolic pathways.

Xiaoli Pan, Shuwei Hu, Yanyong Xu, Raja Gopoju, Yingdong Zhu, Fathima N Cassim Bawa, Hui Wang, Jiayou Wang, Zaid Batayneh, Alyssa Clark, Yuhao Zeng, Li Lin, Xinwen Wang, Liya Yin, Yanqiao Zhang.

   BACKGROUND: Krüppel-like factor 10 (KLF10), a zinc finger transcription factor, plays a pivotal role in modulating TGF-β-mediated cellular processes such as growth, apoptosis, and differentiation. Recent studies have implicated KLF10 in regulating lipid metabolism and glucose homeostasis. This study aimed to elucidate the precise role of hepatic KLF10 in developing metabolic dysfunction-associated steatohepatitis (MASH) in diet-induced obese mice.
METHODS: We investigated hepatic KLF10 expression under metabolic stress and the effects of overexpression or ablation of hepatic KLF10 on MASH development and lipidemia. We also determined whether hepatocyte nuclear factor 4α (HNF4α) mediated the metabolic effects of KLF10.
RESULTS: Hepatic KLF10 was downregulated in MASH patients and genetically or diet-induced obese mice. AAV8-mediated overexpression of KLF10 in hepatocytes prevented Western diet-induced hypercholesterolemia and steatohepatitis, whereas inactivation of hepatocyte KLF10 aggravated Western diet-induced steatohepatitis. Mechanistically, KLF10 reduced hepatic triglyceride and free fatty acid levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis, and reducing hepatic cholesterol levels by promoting bile acid synthesis. KLF10 highly induced HNF4α expression by directly binding to its promoter. The beneficial effect of KLF10 on MASH development was abolished in mice lacking hepatocyte HNF4α. In addition, the inactivation of KLF10 in hepatic stellate cells exacerbated Western diet-induced liver fibrosis by activating the TGF-β/SMAD2/3 pathway.
CONCLUSIONS: Our data collectively suggest that the transcription factor KLF10 plays a hepatoprotective role in MASH development by inducing HNF4α. Targeting hepatic KLF10 may offer a promising strategy for treating MASH.

Keywords:  Bile acid; Cholesterol metabolism; HNF4α; KLF10; MASH

DOI:  https://doi.org/10.1016/j.metabol.2024.155909
J Cell Biochem. 2024 Apr 09.

Irisin influences the in vitro differentiation of human mesenchymal stromal cells, promoting a tendency toward beiging adipogenesis.

Girolamo Di Maio, Nicola Alessio, Alessia Ambrosino, Sura H A Al Sammarraie, Marcellino Monda, Giovanni Di Bernardo.

  Mammals exhibit two distinct types of adipose depots: white adipose tissue (WAT) and brown adipose tissue (BAT). While WAT primarily functions as a site for energy storage, BAT serves as a thermogenic tissue that utilizes energy and glucose consumption to regulate core body temperature. Under specific stimuli such as exercise, cold exposure, and drug treatment, white adipocytes possess a remarkable ability to undergo transdifferentiation into brown-like cells known as beige adipocytes. This transformation process, known as the "browning of WAT," leads to the acquisition of new morphological and physiological characteristics by white adipocytes. We investigated the potential role of Irisin, a 12 kDa myokine that is secreted in mice and humans by skeletal muscle after physical activity, in inducing the browning process in mesenchymal stromal cells (MSCs). A subset of the MSCs possesses the remarkable capability to differentiate into different cell types such as adipocytes, osteocytes, and chondrocytes. Consequently, comprehending the effects of Irisin on MSC biology becomes a crucial factor in investigating antiobesity medications. In our study, the primary objective is to evaluate the impact of Irisin on various cell types engaged in distinct stages of the differentiation process, including stem cells, committed precursors, and preadipocytes. By analyzing the effects of Irisin on these specific cell populations, our aim is to gain a comprehensive understanding of its influence throughout the entire differentiation process, rather than solely concentrating on the final differentiated cells. This approach enables us to obtain insights into the broader effects of Irisin on the cellular dynamics and mechanisms involved in adipogenesis.

Keywords:  Irisin; MSCs; UCP1; adipogenesis; beiging; browning

DOI:  https://doi.org/10.1002/jcb.30565
JCI Insight. 2024 Apr 11. pii: e175629. [Epub ahead of print]

Insulin regulation of regional lipolysis in upper-body obese and lean humans.

Søren Nielsen, Michael D Jensen.

   BACKGROUND: Upper body obesity (UBO) results in insulin resistance with regards to free fatty acid (FFA) release; how this differs by fat depot and sex between UBO and lean adults is unknown. We tested the hypothesis that insulin suppression of FFA release from the splanchnic bed, leg fat and upper body non-splanchnic (UBNS) adipose tissue would be impaired in UBO.
METHODS: Fourteen UBO (7 men, 7 women) and 14 healthy, normal weight (7 men, 7 women) volunteers participated in studies that included femoral artery, femoral vein and hepatic vein catheterization. We then measured leg and splanchnic plasma flow as well as FFA kinetics (using isotopic tracers) under overnight fasting, low- and high-dose insulin infusion using the insulin clamp technique.
RESULTS: We found the expected insulin resistance in UBO; the most quantitatively important difference between UBO and lean adults was greater FFA release from UBNS adipose tissue when plasma insulin concentrations are in the post-prandial, physiological range. There were obesity, but not sex differences in the regulation of splanchnic FFA release and sex differences in the regulation of leg FFA release.
CONCLUSION: Reversing the defects in insulin-regulated UBNS adipose tissue FFA release would have the greatest impact on systemic FFA abnormalities in UBO.
TRIAL REGISTRATION: (not applicable)Funding: These studies were supported by grants DK45343 and DK40484 from the U.S. Public Health Service, and the Novo Nordic Foundation (grant numbers NNF18OC0031804 and NNF16OC0021406) and the Independent Research Fund Denmark (grant number 8020-00420B).

Keywords:  Adipose tissue; Endocrinology; Insulin; Obesity

DOI:  https://doi.org/10.1172/jci.insight.175629
Cell Mol Life Sci. 2024 Apr 10. 81(1): 176

A novel fatty acid analogue triggers CD36-GPR120 interaction and exerts anti-inflammatory action in endotoxemia.

Pierre-Marie Boutanquoi, Amira Sayed Khan, Lidia Cabeza, Lucas Jantzen, Thomas Gautier, Semen Yesylevskyy, Christophe Ramseyer, David Masson, Vincent Van Waes, Aziz Hichami, Naim Akhtar Khan.

  Inflammation is a mediator of a number of chronic pathologies. We synthesized the diethyl (9Z,12Z)-octadeca-9,12-dien-1-ylphosphonate, called NKS3, which decreased lipopolysaccharide (LPS)-induced mRNA upregulation of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) not only in primary intraperitoneal and lung alveolar macrophages, but also in freshly isolated mice lung slices. The in-silico studies suggested that NKS3, being CD36 agonist, will bind to GPR120. Co-immunoprecipitation and proximity ligation assays demonstrated that NKS3 induced protein-protein interaction of CD36 with GPR120in RAW 264.7 macrophage cell line. Furthermore, NKS3, via GPR120, decreased LPS-induced activation of TAB1/TAK1/JNK pathway and the LPS-induced mRNA expression of inflammatory markers in RAW 264.7 cells. In the acute lung injury model, NKS3 decreased lung fibrosis and inflammatory cytokines (IL-1β, IL-6 and TNF-α) and nitric oxide (NO) production in broncho-alveolar lavage fluid. NKS3 exerted a protective effect on LPS-induced remodeling of kidney and liver, and reduced circulating IL-1β, IL-6 and TNF-α concentrations. In a septic shock model, NKS3 gavage decreased significantly the LPS-induced mortality in mice. In the last, NKS3 decreased neuroinflammation in diet-induced obese mice. Altogether, these results suggest that NKS3 is a novel anti-inflammatory agent that could be used, in the future, for the treatment of inflammation-associated pathologies.

Keywords:  Fat; Inflammation; Lipids; Lipopolysaccharide; Taste buds

DOI:  https://doi.org/10.1007/s00018-024-05207-1