Cover Story Current Issue

The high prevalence of obesity is associated with increased mortality because of various comorbidities evoked by an increase in adiposity. Type II diabetes and cardiovascular disease are major medical conditions commonly linked to alterations in the homeostatic pathways that regulate energy homeostasis. As a master regulator of energy balance, the brain integrates peripheral signals and, in turn, modulates feeding behavior and the activity of the autonomic nervous system. The hypothalamus acts as the main hub that receives and integrates peripheral signals.

Mohamed Rouabhi, Deng-Fu Guo, Donald A. Morgan, Zhiyong Zhu, ... Kamal Rahmouni

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Current Issue

Ube2i deletion in adipocytes causes lipoatrophy in mice

Aaron R. Cox, Natasha Chernis, Kang Ho Kim, Peter M. Masschelin, ... Sean M. Hartig

Objective

White adipose tissue (WAT) expansion regulates energy balance and overall metabolic homeostasis. The absence or loss of WAT occurring through lipodystrophy and lipoatrophy contributes to the development of hepatic steatosisand insulin resistance. We previously demonstrated that sole small ubiquitin-like modifier (SUMO) E2-conjugating enzyme Ube2i represses human adipocyte differentiation. The role of Ube2i during WAT development remains unknown.

Methods

To determine how Ube2i impacts body composition and energy balance, we generated adipocyte-specific Ube2i knockout mice (Ube2ia-KO). CRISPR/Cas9 gene editing inserted loxP sites flanking exons 3 and 4 at the Ube2i locus. Subsequent genetic crosses to Adipoq-Cre transgenic mice allowed deletion of Ube2i in white and brown adipocytes. We measured multiple metabolic endpoints that describe energy balance and carbohydrate metabolism in Ube2ia-KO and littermate controls during postnatal growth.

Results

Surprisingly, Ube2ia-KO mice developed hyperinsulinemia and hepatic steatosis. Global energy balance defects emerged from dysfunctional WAT marked by pronounced local inflammation, loss of serum adipokineshepatomegaly, and near absence of major adipose tissue depots. We observed progressive lipoatrophy that commences in the early adolescent period.

Conclusions

Our results demonstrate that Ube2i expression in mature adipocytes allows WAT expansion during postnatal growth. Deletion of Ube2i in fat cells compromises and diminishes adipocyte function that induces WAT inflammation and ectopic lipid accumulation in the liver. Our findings reveal an indispensable role for Ube2iduring white adipocyte expansion and endocrine control of energy balance.

 

Ube2i deletion in adipocytes causes lipoatrophy in mice

Aaron R. Cox, Natasha Chernis, Kang Ho Kim, Peter M. Masschelin, ... Sean M. Hartig

Objective

White adipose tissue (WAT) expansion regulates energy balance and overall metabolic homeostasis. The absence or loss of WAT occurring through lipodystrophy and lipoatrophy contributes to the development of hepatic steatosisand insulin resistance. We previously demonstrated that sole small ubiquitin-like modifier (SUMO) E2-conjugating enzyme Ube2i represses human adipocyte differentiation. The role of Ube2i during WAT development remains unknown.

Methods

To determine how Ube2i impacts body composition and energy balance, we generated adipocyte-specific Ube2i knockout mice (Ube2ia-KO). CRISPR/Cas9 gene editing inserted loxP sites flanking exons 3 and 4 at the Ube2i locus. Subsequent genetic crosses to Adipoq-Cre transgenic mice allowed deletion of Ube2i in white and brown adipocytes. We measured multiple metabolic endpoints that describe energy balance and carbohydrate metabolism in Ube2ia-KO and littermate controls during postnatal growth.

Results

Surprisingly, Ube2ia-KO mice developed hyperinsulinemia and hepatic steatosis. Global energy balance defects emerged from dysfunctional WAT marked by pronounced local inflammation, loss of serum adipokineshepatomegaly, and near absence of major adipose tissue depots. We observed progressive lipoatrophy that commences in the early adolescent period.

Conclusions

Our results demonstrate that Ube2i expression in mature adipocytes allows WAT expansion during postnatal growth. Deletion of Ube2i in fat cells compromises and diminishes adipocyte function that induces WAT inflammation and ectopic lipid accumulation in the liver. Our findings reveal an indispensable role for Ube2iduring white adipocyte expansion and endocrine control of energy balance.

 

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

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