BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice

Choi, Jin Woo; Jo, Anna; Kim, Min; Park, Ho Seon; Chung, Sung Soo; Kang, Shinae; Park, Kyong Soo

doi:10.1007/s00125-015-3836-9

Cited by 26 publications

(22 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We substantiate their data and also provide evidence supporting the necessity of C/EBPα in the regulation of Bnip3 expression. Similar to our results, Choi et al also reported that Bnip3 is critical for adipocyte mitochondrial bioenergetics, but they ascribed this to a Bnip3-related increase in mitochondrial biogenesis (49). We have exhaustively analyzed various indices for mitochondrial content but were unable to find disparities between shCtrl and Bnip3-KD adipocytes.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

A PPARγ-Bnip3 Axis Couples Adipose Mitochondrial Fusion-Fission Balance to Systemic Insulin Sensitivity

et al. 2016

View full text Add to dashboard Cite

Aberrant mitochondrial fission plays a pivotal role in the pathogenesis of skeletal muscle insulin resistance. However, fusion-fission dynamics are physiologically regulated by inherent tissue-specific and nutrient-sensitive processes that may have distinct or even opposing effects with respect to insulin sensitivity. Based on a combination of mouse population genetics and functional in vitro assays, we describe here a regulatory circuit in which peroxisome proliferator–activated receptor γ (PPARγ), the adipocyte master regulator and receptor for the thiazolidinedione class of antidiabetic drugs, controls mitochondrial network fragmentation through transcriptional induction of Bnip3. Short hairpin RNA–mediated knockdown of Bnip3 in cultured adipocytes shifts the balance toward mitochondrial elongation, leading to compromised respiratory capacity, heightened fatty acid β-oxidation-associated mitochondrial reactive oxygen species generation, insulin resistance, and reduced triacylglycerol storage. Notably, the selective fission/Drp1 inhibitor Mdivi-1 mimics the effects of Bnip3 knockdown on adipose mitochondrial bioenergetics and glucose disposal. We further show that Bnip3 is reciprocally regulated in white and brown fat depots of diet-induced obesity and leptin-deficient ob/ob mouse models. Finally, Bnip3−/− mice trade reduced adiposity for increased liver steatosis and develop aggravated systemic insulin resistance in response to high-fat feeding. Together, our data outline Bnip3 as a key effector of PPARγ-mediated adipose mitochondrial network fragmentation, improving insulin sensitivity and limiting oxidative stress.

show abstract

Section: Discussionsupporting

confidence: 91%

“…A study by Choi et al (49) validated Bnip3 as a direct transcriptional target of PPARγ in adipose tissue. We substantiate their data and also provide evidence supporting the necessity of C/EBPα in the regulation of Bnip3 expression.…”

Section: Discussionmentioning

confidence: 99%

A PPARγ-Bnip3 Axis Couples Adipose Mitochondrial Fusion-Fission Balance to Systemic Insulin Sensitivity

et al. 2016

View full text Add to dashboard Cite

show abstract

“…While parkin may be best characterized in the context of mitophagy, several other proteins appear to function in a somewhat similar manner, with their recruitment to mitochondria mediating degradation of the organelle. The role of one such protein, BNip3, was recently investigated in a similar context to the present manuscript . The authors observed an increase in BNip3 expression in 3T3‐L1 adipocytes following rosiglitazone treatment, while the adipose tissues of high‐fat‐diet‐fed and db/db mice exhibited decreased BNip3 expression.…”

Section: Discussionmentioning

confidence: 52%

Parkin‐mediated mitophagy is downregulated in browning of white adipose tissue

Taylor

Gottlieb

2017

Obesity

View full text Add to dashboard Cite

Objective Browning of white adipose tissue (WAT) promotes increased energy expenditure through the action of uncoupling protein 1 (UCP1), and is an attractive target to promote weight loss in obesity. Lowering of mitochondrial membrane potential by UCP1 is uniquely beneficial in this context; in other tissues reduced membrane potential promotes mitochondrial clearance via mitophagy. It is unknown how parkin-mediated mitophagy is regulated in beige adipocytes. Methods The relationship between parkin expression and WAT browning was investigated in 3T3-L1 adipocytes and parkin-deficient male C57BL/6 mice in response to pharmacological browning stimuli. Results Rosiglitazone treatment in 3T3-L1 adipocytes promoted mitochondrial biogenesis, UCP1 expression and mitochondrial uncoupling. Parkin expression was decreased and reduced mitochondrial-associated parkin and p62 indicated a reduction in mitophagy activity. Parkin overexpression prevented mitochondrial remodeling in response to rosiglitazone. In CL 316,243-treated wild-type mice, decreased parkin expression was observed in subcutaneous inguinal WAT, where UCP1 was strongly induced. CL 316,243 treatment weakly induced UCP1 expression in the gonadal depot, where parkin expression was unchanged. In contrast parkin-deficient mice exhibited robust UCP1 expression in gonadal WAT following CL 316,243 treatment. Conclusions WAT browning was associated with a decrease in parkin-mediated mitophagy, and parkin expression antagonized browning of white adipose tissue.

show abstract

“…The images were analyzed with ImageJ version 1.49v software (http://imagej.nih.gov/ij). Electron microscopic image analysis was performed according to a previous report (21).…”

Section: Histological Analysismentioning

confidence: 99%

“…Western blot was performed as previously described (21) with anti-PDX-1, anti-GLUT2, and anti-GAPDH (Sigma-Aldrich) antibodies.…”

Section: Western Blotmentioning

confidence: 99%

β-Cell–Derived Angiopoietin-1 Regulates Insulin Secretion and Glucose Homeostasis by Stabilizing the Islet Microenvironment

et al. 2019

Self Cite

View full text Add to dashboard Cite

Islets are highly vascularized for prompt insulin secretion. Although angiopoietin-1 (Ang1) is a wellknown angiogenic factor, its role in glucose homeostasis remains largely unknown. The objective of this study was to investigate whether and how Ang1 contributes to glucose homeostasis in response to metabolic challenge. We used inducible systemic Ang1 knockout (Ang1 sys2/2) and b-cellspecific Ang1 knockout (Ang1 b-cell2/2) mice fed a high-fat diet for 24 weeks. Although the degree of insulin sensitivity did not differ between Ang1 sys2/2 and Ang1 sys+/+ mice, serum insulin levels were lower in Ang1 sys2/2 mice, resulting in significant glucose intolerance. Similar results were observed in Ang1 b-cell2/2 mice, suggesting a critical role of b-cell-derived Ang1 in glucose homeostasis. There were no differences in b-cell area or vasculature density, but glucosestimulated insulin secretion was significantly decreased, and PDX-1 expression and GLUT2 localization were altered in Ang1 b-cell2/2 compared with Ang1 b-cell+/+ mice. These effects were associated with less pericyte coverage, disorganized endothelial cell ultrastructure, and enhanced infiltration of inflammatory cells and upregulation of adhesion molecules in the islets of Ang1 b-cell2/2 mice. In conclusion, b-cell-derived Ang1 regulates insulin secretion and glucose homeostasis by stabilizing the blood vessels in the islet and may be a novel therapeutic target for diabetes treatment in the future.

show abstract

BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice

Cited by 26 publications

References 50 publications

A PPARγ-Bnip3 Axis Couples Adipose Mitochondrial Fusion-Fission Balance to Systemic Insulin Sensitivity

A PPARγ-Bnip3 Axis Couples Adipose Mitochondrial Fusion-Fission Balance to Systemic Insulin Sensitivity

Parkin‐mediated mitophagy is downregulated in browning of white adipose tissue

β-Cell–Derived Angiopoietin-1 Regulates Insulin Secretion and Glucose Homeostasis by Stabilizing the Islet Microenvironment

Contact Info

Product

Resources

About