Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18 adipocyte-specific knockout (Rab18 AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18 AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18 AKO mice had a moderate increase without ER stress stimulation. Rab18 AKO mice developed insulin resistance and systematic inflammation. Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Group 3 Innate Lymphoid Cells Protect the Host from the Uropathogenic Escherichia coli Infection in the Bladder.

Innate lymphoid cells (ILCs) are crucial in orchestrating immunity and maintaining tissue homeostasis in various barrier tissues, but whether ILCs influence immune responses in the urinary tract remains poorly understood. Here, bladder-resident ILCs are comprehensively explored and identified their unique phenotypic and developmental characteristics. Notably, bladder-resident ILCs rapidly respond to uropathogenic Escherichia coli (UPEC) infection. It is found that ILC3 is necessary for early protection against UPEC infection in the bladder. Mechanistically, UPEC infection leads to interleukin (IL)-1ß production in the bladder via a MyD88-dependent pathway, which promotes ILC3 activation. ILC3-expressed IL-17A further recruits neutrophils and controls UPEC infection in the bladder. Together, these results demonstrate a critical role for bladder ILCs in the host defense against UPEC infection.