Increasing hypothalamic nucleobindin 2 levels and decreasing hypothalamic inflammation in obese male mice via diet and exercise alleviate obesity-associated hypogonadism

Chen, Dequan; Cao, Shicheng; Bo, Chang; Ma, Tie; Gao, Haining; Tong, Yao; Li, Tao; Han, Junchao; Yi, Xuejie

doi:10.1016/j.npep.2018.10.005

Cited by 15 publications

(16 citation statements)

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“…Western blotting Protein lysates from mouse skeletal muscle and C2C12 cells were analysed by western blotting, as previously described [35]. Western blotting [35] was performed at 4°C overnight using primary antibodies against the following proteins: adiponectin, APPL1, PGC-1α, GAPDH (all from Abcam, Cambridge, UK), SIRT1 (Bioss Antibodies, Shanghai, China), and β-Tubulin (Affinity Biosciences, Cincinnati, OH, USA). Antibodies diluted in tris-buffered saline containing 0.05% Tween (TBS-T).…”

Section: Measurement Of Mots-c-related Proteins and Plasma Hormone Levelsmentioning

confidence: 99%

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1–SIRT1–PGC-1α

Guo

et al. 2020

Diabetologia

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Aims/hypothesis Adiponectin stimulates mitochondrial biogenesis through peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a major regulator of mitochondrial biogenesis. MOTS-c (mitochondrial open reading frame of the 12S rRNA) is a biologically active mitochondrial-derived peptide encoded by mitochondrial DNA. It influences the mechanisms of obesity and diabetes. We hypothesised that the adiponectin pathway may regulate the production and/or secretion of MOTS-c in skeletal muscle. We aimed to determine whether exercise and adiponectin affect MOTS-c to improve insulin resistance in mice. Methods To investigate this hypothesis, we used wild-type C57BL/6 mice subjected to high-fat diet, an exercise regimen, and i.p. injection of recombinant mouse adiponectin (Acrp30) or MOTS-c, and adiponectin knockout (Adipoq −/− ) mice (C57BL/6 background) subjected to i.p. injection of Acrp30. C2C12 myotubes were also treated with sirtuin 1 (SIRT1) inhibitor, PGC-1α inhibitor, SIRT1 activator, plasmid-expressed active APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper), pcDNA-SIRT1, or siRNA against APPL1, SIRT1 or PGC-1α. Results In Adipoq -/mice, MOTS-c levels in the plasma and skeletal muscle were downregulated. In C2C12 myotubes, adiponectin increased the mRNA expression of MOTS-c. APPL1 protein level following adiponectin treatment positively correlated with MOTS-c protein and mRNA levels in C2C12 myotubes. SIRT1 overexpression increased the adiponectininduced mRNA and protein expression of MOTS-c, SIRT1 and PGC-1α. Pharmacologic and genetic inhibition of PGC-1α suppressed the increases in MOTS-c mRNA and protein levels induced by SIRT1 overexpression. In mice, plasma and skeletal muscle MOTS-c levels were significantly downregulated following high-fat-diet. Exercise and i.p. Acrp30 or MOTS-c increased MOTS-c levels and adiponectin mRNA and protein expression in the plasma and skeletal muscle. Conclusions/interpretation Our findings showed that the APPL1-SIRT1-PGC-1α pathway regulates the production and/or secretion of skeletal muscle MOTS-c by mediating adiponectin signalling. Our study provides an insight into the cellular and molecular pathways underlying the pathogenesis of diabetes and shows that MOTS-c is a potential novel therapeutic target in the treatment of diabetes. Keywords Adiponectin . Diabetes . Exercise-mediated signalling . Mitochondrial biogenesis . MOTS-c . Skeletal muscle Abbreviations Acrp30 Recombinant mouse adiponectin AMPK AMP-activated protein kinase APPL1 Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 HFD High-fat diet KO Knockout MOTS-c Mitochondrial open reading frame of the 12S rRNA-c mtDNA Mitochondrial DNA PGC-1α Peroxisome proliferator-activated receptor-γ coactivator 1α Electronic supplementary material The online version of this article (

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Section: Measurement Of Mots-c-related Proteins and Plasma Hormone Levelsmentioning

confidence: 99%

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1–SIRT1–PGC-1α

Guo

et al. 2020

Diabetologia

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“…Then, they were randomly divided into (1) HFD group (n = 6, fed with HFD for the final eight weeks), (2) HFD + BAA6 group (n = 6, fed with HFD and treated with BAA6 for the final eight weeks (10 9 CFU/kg per day)), (3) HFD + AKK group (n = 6, fed with HFD and treated with AKK for the final eight weeks (10 9 CFU/kg per day) as positive control). AKK could alleviate obesity [14], which was positively correlated with anti-inflammation [72], as well as the levels of fat browning, fatty acid oxidation, and heat production [73]. BAA6 and AKK were suspended in 0.9% saline solution, then administrated by oral gavage daily from the 10th week.…”

Section: Animals and Dietsmentioning

confidence: 99%

“…lactis I-2494 was shown to be able to decrease body weight gain and balance gut microbiota composition [13]. It was reported that Akkermansia muciniphila (AKK) could decrease the adipose tissue mass and alleviate obesity [14,15]. At present, the mechanisms of probiotics improving obesity are mainly related to fat metabolism, insulin sensitivity, and intestinal microbiota composition.…”

Section: Introductionmentioning

confidence: 99%

Bifidobacterium animalis subsp. lactis A6 Alleviates Obesity Associated with Promoting Mitochondrial Biogenesis and Function of Adipose Tissue in Mice

Huo

Wang

et al. 2020

Molecules

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Probiotics are widely known for their health benefits. Mitochondrial dysfunction is related to obesity. The aim of this study was to illuminate whether Bifidobacterium animalis subsp. lactis A6 (BAA6) could improve obesity due to increased mitochondrial biogenesis and function of adipose tissues. Four-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 17 weeks. For the final eight weeks, the HFD group was divided into three groups including HFD, HFD with BAA6 (HFD + BAA6 group), and HFD with Akkermansia muciniphila (AKK) (HFD + AKK group as positive control). The composition of the microbiota, serum lipopolysaccharides (LPS), and mitochondrial biosynthesis and function of epididymal adipose tissues were measured. Compared with the HFD group, body weight, relative fat weight, the relative abundance of Oscillibacter and Bilophila, and serum LPS were significantly decreased in the HFD + BAA6 and HFD + AKK groups (p < 0.05). Furthermore, the addition of BAA6 and AKK increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (by 21.53- and 18.51-fold), estrogen-related receptor α (ERRα) (by 2.83- and 1.24-fold), and uncoupling protein-1 (UCP-1) (by 1.51- and 0.60-fold) in epididymal adipose tissues. Our results suggest that BAA6 could improve obesity associated with promoting mitochondrial biogenesis and function of adipose tissues in mice.

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“…After the obesity model was successfully established, exercise interventions for OE and ODE were carried out for 8 weeks, using treadmill running ( 22 ); the first 3 weeks constituted an incremental load adaptive training of 6 days/week, with a slope of 0%, starting speed of 10 m/min, and duration of 20 min/day. Thereafter, the training period was increased by 4 min and the running speed by 1 m/min, on average every day, based on previous reports and the state of the mice ( 23 ). The load reached 25 m/min and 90 min/day from the fourth week and was continuously applied until the eighth week.…”

Section: Methodsmentioning

confidence: 99%

Effects of exercise and dietary intervention on muscle, adipose tissue, and blood IRISIN levels in obese male mice and their relationship with the beigeization of white adipose tissue

et al. 2022

Endocrine Connections

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Background: Obesity is a growing problem worldwide, and newer therapeutic strategies to combat it are urgently required. This study aimed to analyze the effect of diet and exercise interventions on energy balance in mice and elucidate the mechanism of the peroxisome proliferator-activated receptor-gamma co-activator-1-alpha-IRISIN-uncoupling protein-1 (PGC-1α-IRISIN-UCP-1) pathway in the beigeization of white adipose tissue. Methods: Four-week-old male C57BL/6 mice were randomly divided into normal (NC) and high-fat diet (HFD) groups. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control(OC), obesity diet control (OD), obesity exercise (OE), and obesity diet control exercise (ODE) groups. Mice in OE and ODE performed moderate-load treadmill exercises and the diet constituted 70% of the food intake of the OC group for 8 weeks. Results: Long-term HFD inhibits white adipose tissue beigeization by downregulating PGC-1α-IRISIN-UCP-1 in the adipose tissue and skeletal muscles. Eight weeks of exercise and dietary interventions alleviated obesity-induced skeletal muscle and adipose tissue PGC-1α-IRISIN-UCP-1 pathway downregulation promoted white adipose tissue beigeization and reduced body adipose tissue. The effects of the combined intervention were better than those of single interventions. Conclusions: Diet and exercise intervention after obesity and obesity itself may affect the beigeization of WAT by downregulating/upregulating the expression/secretion of skeletal muscle and adipose PGC-1α-IRISIN, thereby influencing the regulation of body weight. The effects of the combined intervention were better than those of single interventions.

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Increasing hypothalamic nucleobindin 2 levels and decreasing hypothalamic inflammation in obese male mice via diet and exercise alleviate obesity-associated hypogonadism

Cited by 15 publications

References 49 publications

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1–SIRT1–PGC-1α

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1–SIRT1–PGC-1α

Bifidobacterium animalis subsp. lactis A6 Alleviates Obesity Associated with Promoting Mitochondrial Biogenesis and Function of Adipose Tissue in Mice

Effects of exercise and dietary intervention on muscle, adipose tissue, and blood IRISIN levels in obese male mice and their relationship with the beigeization of white adipose tissue

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