Discovery and functional assessment of a novel adipocyte population driven by intracellular Wnt/β-catenin signaling in mammals

Zhi, Liu; Tian, Chen; Zhang, Sicheng; Yang, Tianfang; Gong, Yun; Deng, Hong‐Wen; Bai, Ding; Tian, Weidong; Chen, YiPing

doi:10.7554/elife.77740

Cited by 7 publications

(3 citation statements)

References 74 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Beige adipocytes are unlikely to be uniform in origin and may be enriched in adipose depots through distinct mechanisms, including de novo differentiation of more than one progenitor cell type, conversion from mature adipocytes, or proliferation of progenitors or mature cells ( 3 ). Aligned with our results, a study published at the time of this writing used a β-catenin reporter system to show that a distinct population of beige adipocytes is driven by enhanced WNT signaling ( 70 ). It is also worth noting that a recent study tracing the origin of cold-induced beige fat suggests that the proliferative capacity of some APCs is a critical determinant of beiging ( 67 ).…”

Section: Discussionsupporting

confidence: 83%

A PPARγ/long noncoding RNA axis regulates adipose thermoneutral remodeling in mice

Zhang,

Cui,

et al. 2023

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

Interplay between energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of specialized niche, adipocytes require the activity of the nuclear receptor PPARγ for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ; however, the molecular mechanisms by which PPARγ licenses white adipose tissue to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ/long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity. Pharmacologic inhibition or genetic deletion of the lncRNA Lexis enhances uncoupling protein 1–dependent (UCP1-dependent) and -independent thermogenesis. Adipose-specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT that preserves white adipose tissue plasticity.

show abstract

Section: Discussionsupporting

confidence: 83%

A PPARγ/long noncoding RNA axis regulates adipose thermoneutral remodeling in mice

Zhang,

Cui,

et al. 2023

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

show abstract

“…To investigate whether adipogenic Dkk1 plays a role in bone homeostasis, we generated Dkk1 fl/fl ;AdipoQcre mice which specifically target adipocytes ( 28 , 29 ). At 12 weeks of age, male Dkk1 fl/fl ;AdipoQcre mice showed a similar body weight ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice

Daamouch,

Thiele,

Hofbauer

et al. 2023

Endocrine Connections

View full text Add to dashboard Cite

Obesity has been linked to reduced bone strength, and the canonical Wnt signaling pathway plays a crucial role in regulating mesenchymal stem cell differentiation into either osteoblasts or adipocytes. Previous research has shown that obesity-induced upregulation of Dkk1, a Wnt inhibitor produced by osteoblasts, drives bone loss. However, the role of adipocyte-produced Dkk1 in bone remodeling and obesity-induced bone loss remains unclear. In this study, we investigated the influence of adipogenic Dkk1 on bone homeostasis and obesity-induced bone loss in mice. Using tamoxifen administration, we induced deletion of Dkk1 in adipocytes in male Dkk1fl/fl;AdipoQcreERT2 (Dkk1 cKO) mice and fed Dkk1fl/fl;AdipoQcre-positive mice and controls a high-fat diet (HFD) for 12 weeks. Bone and fat mass were analyzed at 12 and 20 weeks of age. In this study we found that 12-week-old male mice without adipogenic Dkk1 had a significant increase in trabecular bone volume in the vertebrae and femoral bones. However, there was no difference in bone volume between controls and Dkk1fl/fl;AdipoQcre-positive mice at 20 weeks of age. Additionally, Dkk1fl/fl;AdipoQcre-positive mice were not protected from HFD-induced bone loss. Even though Sost, another important Wnt inhibitor, was expressed at lower levels in bone from Dkk1-deficient mice fed with HFD compared to Dkk1-sufficient mice, this did not prevent the HFD-induced suppression of bone formation. Therefore, adipogenic Dkk1 may play a transient role in bone mass regulation during adolescence, but it does not contribute to bone homeostasis or obesity-induced bone loss later in life.

show abstract

“…The role of β‐catenin in adipocyte insulin resistance is unclear. Cultured three T3‐L1 adipocytes appear to require β‐catenin for optimal glucose uptake (Dissanayake et al, 2018), and a subpopulation of adipocytes with enhanced Wnt‐signaling positively contribute to glucose handling (Liu et al, 2022). However, adipocytes‐specific deletion of β‐catenin in mice results in improved insulin sensitivity and reduced obesity (Bagchi et al, 2020; Chen et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A role for β‐catenin in diet‐induced skeletal muscle insulin resistance

Masson

Dissanayake

Broome

et al. 2023

Physiological Reports

View full text Add to dashboard Cite

A central characteristic of insulin resistance is the impaired ability for insulin to stimulate glucose uptake into skeletal muscle. While insulin resistance can occur distal to the canonical insulin receptor‐PI3k‐Akt signaling pathway, the signaling intermediates involved in the dysfunction are yet to be fully elucidated. β‐catenin is an emerging distal regulator of skeletal muscle and adipocyte insulin‐stimulated GLUT4 trafficking. Here, we investigate its role in skeletal muscle insulin resistance. Short‐term (5‐week) high‐fat diet (HFD) decreased skeletal muscle β‐catenin protein expression 27% (p = 0.03), and perturbed insulin‐stimulated β‐cateninS552 phosphorylation 21% (p = 0.009) without affecting insulin‐stimulated Akt phosphorylation relative to chow‐fed controls. Under chow conditions, mice with muscle‐specific β‐catenin deletion had impaired insulin responsiveness, whereas under HFD, both mice exhibited similar levels of insulin resistance (interaction effect of genotype × diet p < 0.05). Treatment of L6‐GLUT4‐myc myocytes with palmitate lower β‐catenin protein expression by 75% (p = 0.02), and attenuated insulin‐stimulated β‐catenin phosphorylationS552 and actin remodeling (interaction effect of insulin × palmitate p < 0.05). Finally, β‐cateninS552 phosphorylation was 45% lower in muscle biopsies from men with type 2 diabetes while total β‐catenin expression was unchanged. These findings suggest that β‐catenin dysfunction is associated with the development of insulin resistance.

show abstract

Discovery and functional assessment of a novel adipocyte population driven by intracellular Wnt/β-catenin signaling in mammals

Cited by 7 publications

References 74 publications

A PPARγ/long noncoding RNA axis regulates adipose thermoneutral remodeling in mice

A PPARγ/long noncoding RNA axis regulates adipose thermoneutral remodeling in mice

Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice

A role for β‐catenin in diet‐induced skeletal muscle insulin resistance

Contact Info

Product

Resources

About