Leptin as a key regulator of the adipose organ

AbstractLeptin is a hormone primarily produced by the adipose tissue in proportion to the size of fat stores, with a primary function in the control of lipid reserves. Besides adipose tissue, leptin is also produced by other tissues, such as the stomach, placenta, and mammary gland. Altogether, leptin exerts a broad spectrum of short, medium, and long-term regulatory actions at the central and peripheral levels, including metabolic programming effects that condition the proper development and function of the adipose organ, which are relevant for its main role in energy homeostasis. Comprehending how leptin regulates adipose tissue may provide important clues to understand the pathophysiology of obesity and related diseases, such as type 2 diabetes, as well as its prevention and treatment. This review focuses on the physiological and long-lasting regulatory effects of leptin on adipose tissue, the mechanisms and pathways involved, its main outcomes on whole-body physiological homeostasis, and its consequences on chronic diseases.

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DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

Nature Communications ◽

10.1038/s41467-020-20665-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Haiyan Zhou ◽

Xinyi Peng ◽

Jie Hu ◽

Liwen Wang ◽

Hairong Luo ◽

...

Keyword(s):

T Cells ◽

Adipose Tissue ◽

T Cell ◽

Energy Homeostasis ◽

Metabolic Diseases ◽

Therapeutic Potential ◽

Whole Body ◽

Brown Adipose ◽

Ifn Γ ◽

Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

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Use of a Highly Antioxidant Diet in the Regulation of Adipose Tissue Secretion in Patients after the BIB Procedure

Foods ◽

10.3390/foods10051108 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1108

Author(s):

Edyta Balejko ◽

Jerzy Balejko

Keyword(s):

Adipose Tissue ◽

Immune Modulation ◽

Energy Homeostasis ◽

Secretory Activity ◽

Diet Therapy ◽

Total Polyphenol ◽

Reducing Ability ◽

Bariatric Patients ◽

Antioxidant Diet

Obesity is a global problem. The secretory activity of adipose tissue causes inflammation and disturbs metabolic parameters. Low-invasive bariatric procedures are an alternative to surgical treatment, especially in individuals who do not qualify for surgery or in whom conservative treatment does not bring the expected results. The diets designed for bariatric patients contained an increased proportion of bioflavonoids. The dietary components were carefully selected to provide anti-inflammatory effects. The experimental diets showed an antioxidant capacity (TEAC) of 433–969 µM TE/100 g or 100 mL, reducing ability (FRAP) of 13–58 µM TE/100 g or 100 mL, and total polyphenol content of 80–250 mg catechins/100 g or 100 mL. Lower levels of adipocytokines were obtained in the blood of patients following the diet. The results of the present study showed the participation of some adipocytokines in the regulation of energy homeostasis, lipid metabolism, glucose level, blood pressure and inflammation. Diet therapy should yield positive results in the long term, with the possibility of using immune modulation in personalized therapy for metabolic syndrome.

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Effect of Long-Term Whole Body Vibration Training on Visceral Adipose Tissue: A Preliminary Report

Obesity Facts ◽

10.1159/000301785 ◽

2010 ◽

Vol 3 (2) ◽

pp. 7-7 ◽

Cited By ~ 49

Author(s):

Dirk Vissers ◽

An Verrijken ◽

Ilse Mertens ◽

Caroline Van Gils ◽

Annemie Van de Sompel ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Preliminary Report ◽

Whole Body Vibration ◽

Whole Body ◽

Body Vibration ◽

Vibration Training ◽

Whole Body Vibration Training ◽

Visceral Adipose

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Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1909917116 ◽

2019 ◽

Vol 116 (47) ◽

pp. 23822-23828 ◽

Cited By ~ 8

Author(s):

Shintaro Yamaguchi ◽

Michael P. Franczyk ◽

Maria Chondronikola ◽

Nathan Qi ◽

Subhadra C. Gunawardana ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Metabolism ◽

Cold Exposure ◽

Energy Homeostasis ◽

Lipolytic Activity ◽

Whole Body ◽

Brown Adipocyte ◽

Nicotinamide Phosphoribosyltransferase ◽

Adaptive Thermogenesis ◽

Body Energy

Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD+ metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) and brown adipocyte-specific Nampt knockout (BANKO) mice because NAMPT is the rate-limiting NAD+ biosynthetic enzyme. We found ANKO mice, which lack NAMPT in both BAT and WAT, had impaired gene programs involved in thermogenesis and mitochondrial function in BAT and a blunted thermogenic (rectal temperature, BAT temperature, and whole-body oxygen consumption) response to acute cold exposure, prolonged fasting, and administration of β-adrenergic agonists (norepinephrine and CL-316243). In addition, the absence of NAMPT in WAT markedly reduced adrenergic-mediated lipolytic activity, likely through inactivation of the NAD+–SIRT1–caveolin-1 axis, which limits an important fuel source fatty acid for BAT thermogenesis. These metabolic abnormalities were rescued by treatment with nicotinamide mononucleotide (NMN), which bypasses the block in NAD+ synthesis induced by NAMPT deficiency. Although BANKO mice, which lack NAMPT in BAT only, had BAT cellular alterations similar to the ANKO mice, BANKO mice had normal thermogenic and lipolytic responses. We also found NAMPT expression in supraclavicular adipose tissue (where human BAT is localized) obtained from human subjects increased during cold exposure, suggesting our finding in rodents could apply to people. These results demonstrate that adipose NAMPT-mediated NAD+ biosynthesis is essential for regulating adaptive thermogenesis, lipolysis, and whole-body energy metabolism.

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Mitochondrial form, function and signalling in aging

Biochemical Journal ◽

10.1042/bcj20160451 ◽

2016 ◽

Vol 473 (20) ◽

pp. 3421-3449 ◽

Cited By ~ 18

Author(s):

Ignacio Amigo ◽

Fernanda M. da Cunha ◽

Maria Fernanda Forni ◽

Wilson Garcia-Neto ◽

Pâmela A. Kakimoto ◽

...

Keyword(s):

Mammalian Cells ◽

Energy Homeostasis ◽

Cell Types ◽

Redox Balance ◽

Whole Body ◽

Model Organisms ◽

Resistance To Stress ◽

Whole Body Metabolism ◽

And Function ◽

Different Characteristics

Aging is often accompanied by a decline in mitochondrial mass and function in different tissues. Additionally, cell resistance to stress is frequently found to be prevented by higher mitochondrial respiratory capacity. These correlations strongly suggest mitochondria are key players in aging and senescence, acting by regulating energy homeostasis, redox balance and signalling pathways central in these processes. However, mitochondria display a wide array of functions and signalling properties, and the roles of these different characteristics are still widely unexplored. Furthermore, differences in mitochondrial properties and responses between tissues and cell types, and how these affect whole body metabolism are also still poorly understood. This review uncovers aspects of mitochondrial biology that have an impact upon aging in model organisms and selected mammalian cells and tissues.

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Monocyte Chemoattractant Protein-1 in Subcutaneous Abdominal Adipose Tissue: Characterization of Interstitial Concentration and Regulation of Gene Expression by Insulin

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-2814 ◽

2007 ◽

Vol 92 (7) ◽

pp. 2688-2695 ◽

Cited By ~ 38

Author(s):

Giuseppe Murdolo ◽

Ann Hammarstedt ◽

Madeléne Sandqvist ◽

Martin Schmelz ◽

Christian Herder ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Regulation Of Gene Expression ◽

Whole Body ◽

Mrna Levels ◽

Abdominal Adipose Tissue ◽

Monocyte Chemoattractant Protein 1 ◽

Monocyte Chemoattractant ◽

Monocyte Chemoattractant Protein ◽

Adipose Organ

Abstract Context: The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated in obesity-associated chronic inflammation, insulin resistance, and atherosclerosis. Objectives: The objectives of this study were to: 1) characterize the interstitial levels and the gene expression of MCP-1 in the sc abdominal adipose tissue (SCAAT), 2) elucidate the response of MCP-1 to acute hyperinsulinemia, and 3) determine the relationship between MCP-1 and arterial stiffness. Design: Nine lean (L) and nine uncomplicated obese (OB) males were studied in the fasting state and during a euglycemic-hyperinsulinemic clamp combined with the microdialysis technique. Interstitial and serum MCP-1 (iMCP-1 and sMCP-1, respectively) levels, pulse wave analysis, and SCAAT biopsies were characterized at baseline and after hyperinsulinemia. Results: OB showed elevated sMCP-1 (P < 0.01) but similar iMCP-1 levels as compared with L. Basal iMCP-1 concentrations were considerably higher than sMCP-1 (P < 0.0001), and a gradient between iMCP-1 and sMCP-1 levels was maintained throughout the hyperinsulinemia. At baseline, SCAAT gene expression profile revealed a “co-upregulation” of MCP-1, MCP-2, macrophage inflammatory protein-1α, and CD68 in OB, and whole-body glucose disposal inversely correlated with the MCP-1 gene expression. After hyperinsulinemia, MCP-1 and MCP-2 mRNA levels significantly increased in L, but not in OB. Finally, sMCP-1 excess in the OB positively correlated with the stiffer vasculature. Conclusions: These observations demonstrate similar interstitial concentrations and a differential gene response to hyperinsulinemia of MCP-1 in the SCAAT from L and OB individuals. In human obesity, we suggest the SCAAT MCP-1 gene overexpression as a biomarker of an “inflamed” adipose organ and impaired glucose metabolism.

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Regulation of Adipose Differentiation by Fructose and GluT5

Molecular Endocrinology ◽

10.1210/me.2012-1122 ◽

2012 ◽

Vol 26 (10) ◽

pp. 1773-1782 ◽

Cited By ~ 30

Author(s):

Li Du ◽

Anthony P. Heaney

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Energy Homeostasis ◽

Adipocyte Differentiation ◽

Early Stage ◽

Whole Body ◽

Wild Type ◽

Embryonic Fibroblasts ◽

Fructose Intake ◽

Adipose Differentiation

Abstract Adipose tissue is an important metabolic organ that is crucial for whole-body insulin sensitivity and energy homeostasis. Highly refined fructose intake increases visceral adiposity although the mechanism(s) remain unclear. Differentiation of preadipocytes to mature adipocytes is a highly regulated process that is associated with characteristic sequential changes in adipocyte gene expression. We demonstrate that fructose treatment of murine 3T3-L1 cells incubated in standard differentiation medium increases adipogenesis and adipocyte-related gene expression. We further show that the key fructose transporter, GluT5, is expressed in early-stage adipocyte differentiation but is not expressed in mature adipocytes. GluT5 overexpression or knockdown increased and decreased adipocyte differentiation, respectively, and treatment of 3T3-L1 cells with a specific GluT5 inhibitor decreased adipocyte differentiation. Epidymal white adipose tissue was reduced in GluT5−/− mice compared with wild-type mice, and mouse embryonic fibroblasts derived from GluT5−/− mice exhibited impaired adipocyte differentiation. Taken together, these results demonstrate that fructose and GluT5 play an important role in regulating adipose differentiation.

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Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression

International Journal of Molecular Sciences ◽

10.3390/ijms21218308 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8308

Author(s):

Ming-Ling Chang ◽

Zinger Yang ◽

Sien-Sing Yang

Keyword(s):

Adipose Tissue ◽

Energy Homeostasis ◽

Whole Body ◽

Low Grade ◽

Colon Polyps ◽

Alcoholic Fatty Liver ◽

Global Epidemic ◽

Markers Of Inflammation ◽

Digestive Diseases ◽

Digestive Cancers

Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.

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Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues

Communications Biology ◽

10.1038/s42003-020-0965-6 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Asma Ayari ◽

Manuel Rosa-Calatrava ◽

Steve Lancel ◽

Johanna Barthelemy ◽

Andrés Pizzorno ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Influenza A ◽

Energy Homeostasis ◽

Influenza Infection ◽

Subcutaneous Fat ◽

Whole Body ◽

Glucose And Lipid Metabolism ◽

The Impact

AbstractLike all obligate intracellular pathogens, influenza A virus (IAV) reprograms host cell’s glucose and lipid metabolism to promote its own replication. However, the impact of influenza infection on white adipose tissue (WAT), a key tissue in the control of systemic energy homeostasis, has not been yet characterized. Here, we show that influenza infection induces alterations in whole-body glucose metabolism that persist long after the virus has been cleared. We report depot-specific changes in the WAT of IAV-infected mice, notably characterized by the appearance of thermogenic brown-like adipocytes within the subcutaneous fat depot. Importantly, viral RNA- and viral antigen-harboring cells are detected in the WAT of infected mice. Using in vitro approaches, we find that IAV infection enhances the expression of brown-adipogenesis-related genes in preadipocytes. Overall, our findings shed light on the role that the white adipose tissue, which lies at the crossroads of nutrition, metabolism and immunity, may play in influenza infection.

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