BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle

Wood, John; Tse, Margaret Chui Ling; Yang, Xiuying; Brobst, Daniel; Liu, Zhixue; Pang, Brian Pak Shing; Chan, Wing Suen; Zaw, Aung Moe; Chow, Billy K. C.; Ye, Keqiang; Lee, Chi Wai; Chan, Chi Bun

doi:10.1016/j.metabol.2018.06.007

Cited by 49 publications

(41 citation statements)

References 42 publications

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“…At this time point, plasma adiponectin levels were not significantly different between groups (Figure 2E). male metabolic health, in the context of a HFD, as the previous studies did not in these parameters in male mice [21,52]. Apart from reductions in hepatic lipid accumulation and leptin levels, DHF-fed females had a markedly reduced appearance of crown-like structures in their gonadal adipose depots ( Figure 3A), suggesting decreased adipose inflammation.…”

Section: Oral Dhf Attenuates Weight Gain and Adiposity In Hfd-fed Femmentioning

confidence: 74%

“…Crown-like structures and F4/80 staining appeared to be elevated in adipose of DHF-fed males ( Figure 3A,B). This is the first report of a potentially detrimental effect of DHF on male metabolic health, in the context of a HFD, as the previous studies did not investigate these parameters in male mice [21,52].…”

Section: Oral Dhf Attenuates Weight Gain and Adiposity In Hfd-fed Femmentioning

confidence: 85%

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Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

Sharma

Kumaraswamy

et al. 2021

Nutrients

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7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.

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Section: Oral Dhf Attenuates Weight Gain and Adiposity In Hfd-fed Femmentioning

confidence: 74%

Section: Oral Dhf Attenuates Weight Gain and Adiposity In Hfd-fed Femmentioning

confidence: 85%

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

Sharma

Kumaraswamy

et al. 2021

Nutrients

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“…BDNF was shown to activate the AMP-activated protein kinase (AMPK) and enhance fatty acid oxidation, 11) and it triggers the AMPK/CREB/ PGC-1α pathways to increase cellular respiration by promoting mitochondrial biogenesis in skeletal muscle. 13) The depletion of BDNF in C2C12 myoblasts decreased the level of phosphorylation of AMPK and PGC-1α proteins. 39) We recently reported that BDNF was reduced in the skeletal muscle of a murine model of HF after myocardial infarction, and that the administration of human recombinant BDNF ameliorated the reduction of the endurance exercise capacity and improved the mitochondrial respiration of the skeletal muscle.…”

Section: Discussionmentioning

confidence: 98%

“…11) Exercise training can increase the serum level of BDNF, 12) and BDNF is involved in mitochondrial biogenesis and fatty acid metabolism in skeletal muscle. 13) The skeletal muscles were recently reported to secrete various cytokines and growth factors (collectively called myokines) to regulate their mass and/or function, 14) and BDNF is thus considered one of the myokines.…”

mentioning

confidence: 99%

Serum Brain-Derived Neurotrophic Factor Levels Are Associated with Skeletal Muscle Function but Not with Muscle Mass in Patients with Heart Failure

et al. 2020

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Heart failure (HF) is associated with aberrant skeletal muscle impairments, which are closely linked to the severity of HF. A low level of brain-derived neurotrophic factor (BDNF), a myokine produced in the skeletal muscle, is known to be involved in reduced exercise capacity and poor prognosis in HF. However, little is known about the factors or conditions of skeletal muscle associated with BDNF levels. We investigated the association between serum BDNF levels and the skeletal muscle mass and function in HF patients (n = 60, 63 ± 13 years) and age-matched controls (n = 29, 61 ± 16 years). The serum BDNF level was significantly lower in the HF patients compared to the controls (24.9 ± 0.9 versus 28.6 ± 1.3, P = 0.021). In a univariate analysis, BDNF was significantly correlated with the peak oxygen uptake, estimated glomerular filtration rate, 10-m gait speed, and muscle strength, but not with the body mass index or lean mass in the HF group. A multiple linear regression analysis revealed that BDNF was independently associated with muscle strength (β-coefficient = 2.80, 95%CI: 1.89-11.8, P = 0.008). Serum BDNF levels were associated with exercise capacity and skeletal muscle function, but not with muscle mass. These novel findings may suggest that BDNF production is controlled by muscle function and activity and consequently regulates exercise capacity, highlighting the importance of adequate training regarding skeletal muscle in HF patients.

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“…The relationship between WAT-and BAT-ASC lipid metabolism also requires additional research. Mitochondria are central powerhouses and the major fatty acid oxidation sites in cells, so the improper functioning of mitochondria is a fundamental cause of obesity [Wood et al, 2018]. The mitochondrial membrane potential was also significantly decreased in aged ASCs, and it was possible that mitochondrial dysfunction contributed to lipid accumulation with aging.…”

Section: Discussionmentioning

confidence: 99%

Impact of Aging on the Characterization of Brown and White Adipose Tissue-Derived Stem Cells in Mice

Zhang

Wang

et al. 2020

Cells Tissues Organs

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Adipose tissue enriched with adipose tissue-derived stem cells (ASCs) is often used for stem cell-based therapies. However, the characteristics of ASCs from different types of adipose tissue have varying biochemical and functional properties. We aimed to investigate how age affected the biological and functional characteristics of ASCs from brown (BAT) and white adipose tissue (WAT). ASCs were obtained and cultured from mouse BAT and WAT at different ages: young (2 months of age) and older mice (22 months of age). Mesenchymal markers were characterized by flow cytometry, and cell proliferation, apoptosis, differentiation potential, senescence, and metabolism were then determined. The percentage of WAT was higher in elderly mice, and the percentage of BAT was higher in young mice. All ASC sample phenotypes were characterized as CD29+/CD44+/CD105+/CD45-; the proliferation rate was not statistically different among all age groups. However, the number of senescent cells and the percentage of apoptosis in elderly mouse ASCs were significantly increased, and the ability of osteogenic and lipogenic differentiation was decreased in these same animals. In addition, ASCs from young mice were more inclined to undergo osteogenic differentiation, especially BAT-ASCs, whose gene expression of fat-consuming components was also significantly higher than of WAT-ASCs. The results indicated that ASCs derived from both WAT and BAT possessed different characteristics of fat metabolism and cell differentiation relative to the osteo-and adipolineages. In particular, because BAT-ASCs from young mice contributed to fat consumption, if used for cell grafting, they may potentially be attractive vehicles for treating obesity.

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BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle

Cited by 49 publications

References 42 publications

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

Serum Brain-Derived Neurotrophic Factor Levels Are Associated with Skeletal Muscle Function but Not with Muscle Mass in Patients with Heart Failure

Impact of Aging on the Characterization of Brown and White Adipose Tissue-Derived Stem Cells in Mice

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