Adiponectin preserves metabolic fitness during aging

  1. Na Li
  2. Shangang Zhao
  3. Zhuzhen Zhang
  4. Yi Zhu
  5. Christy M Gliniak
  6. Lavanya Vishvanath
  7. Yu A An
  8. May-yun Wang
  9. Yingfeng Deng
  10. Qingzhang Zhu
  11. Bo Shan
  12. Amber Sherwood
  13. Toshiharu Onodera
  14. Orhan K Oz
  15. Ruth Gordillo
  16. Rana K Gupta
  17. Ming Liu
  18. Tamas L Horvath
  19. Vishwa Deep Dixit
  20. Philipp E Scherer  Is a corresponding author
  1. Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, United States
  2. Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, China
  3. Department of Radiology, University of Texas Southwestern Medical Center, United States
  4. Department of Comparative Medicine and Immunobiology, Yale School of Medicine, United States
  5. Yale Center for Research on Aging, Yale School of Medicine, United States
  6. Department of Cell Biology, The University of Texas Southwestern Medical Center, United States
6 figures, 1 table and 3 additional files

Figures

Figure 1 with 1 supplement
Lack of adiponectin (APN) in aging mice shortens lifespan.

(A) Kaplan–Meier survival curves for wild-type (WT) and adiponectin null (APN-KO) mice on chow diet. (B) Kaplan–Meier survival curves for WT and APN-KO mice on high-fat diet (HFD). (C) Median …

Figure 1—figure supplement 1
Mouse models used for longevity studies: adiponectin null (APN-KO) mice and adiponectin transgenic (ΔGly) mice.

(A) Experimental strategy for longevity experiments. (B) Diagram of the aging process. Lifespan and healthspan are always strongly coupled. (C) Circulating adiponectin levels measured in 50-week-old …

Figure 2 with 1 supplement
Lack of adiponectin (APN) in aging mice worsens glucose and lipid homeostasis.

(A) Body weights during aging processes for wild-type (WT) and adiponectin null (APN-KO) mice fed on chow diet. (B) Body weights during aging processes for WT and APN-KO mice fed on high-fat diet …

Figure 2—figure supplement 1
Body composition of wild-type (WT) mice and adiponectin null (APN-KO) mice.

(A) Fat mass, lean mass, and relative subcutaneous, visceral, and brown fat pad weights of 140-weeks old WT(n=5) and APN-KO (n=5) mice fed chow diet or 100-week-old WT (n = 5–7) and APN-KO mice (n = …

Deletion of adiponectin (APN) in aged mice exacerbates functional decline.

(A) H&E staining of an Epi fat depot of 20-week-old and 100-week-old wild-type (WT) and adiponectin null (APN-KO) mice fed on high-fat diet (HFD) or 140-week-old WT and APN-KO mice on chow diet. (B) …

Figure 4 with 1 supplement
Absence of adiponectin (APN) in aged mice exacerbates inflammation and accelerates aging.

(A) Expression of inflammatory markers in epididymal fat depots of 140-week-old wild-type (WT) and adiponectin null (APN-KO) mice fed on chow diet and 100-week-old WT and APN-KO fed on HFD(n = 10 …

Figure 4—figure supplement 1
Adiponectin deficiency in aged mice exacerbates inflammation and accelerates aging.

(A) Expression of inflammatory and fibrosis markers in liver of 140-week-old wild-type (WT) and adiponectin null (APN-KO) mice fed on chow diet (n = 7 for WT, n = 7 for APN-KO mice). (B) Serum …

Increasing adiponectin protects against aging-induced metabolic disturbance.

(A) Kaplan–Meier survival curves for controls and ΔGly mice on chow diet. Median survival time and maximum lifespan for each cohort. n denotes the number of mice per group. p-Values were determined …

Old adiponectin overexpressing mice exhibit improved glucose and lipid homeostasis.

(A) H&E staining of SubQ fat depot and Epi fat depot of 140-week-old controls and ΔGly mice fed on chow diet. (B) Mac2 staining of epididymal fat sections in 140-week-old controls and ΔGly mice. (C) …

Tables

Key resources table
Reagent type
(species) or resource
DesignationSource or referenceIdentifiersAdditional information
Genetic reagent (Mus musculus)WT C57BL/6JJackson LaboratoryJAX 000664
RRID:IMSR_JAX:000664
N/A
Genetic reagent (Mus musculus)APN-KOPMID:16326714N/AN/A
Genetic reagent (Mus musculus)ΔGlyPMID:14576179N/AN/A
Chemical compound, drugTRIzolTM ReagentThermo FisherCat# 15596018N/A
Chemical compound, drugInsulinEli LillyProduct ID: A10008415N/A
Chemical compound, drugDulbecco’s phosphate buffered salineSigma-AldrichCat# D806552N/A
Chemical compound, drugHigh-fat diet (HFD)Research DietsCat# D12492N/A
Chemical compound, drugDAPILife TechnologyCat# P36941N/A
Chemical compound, drugBovine serum albuminSigmaCat# A9418N/A
Commercial assay or kitAdiponectin ELISA kitInvitrogenCat# EZMADP-60K
RRID:AB_2651034
N/A
Commercial assay or kitInsulin ELISA Jumbo kitALPCOCat# 80-INSMS-E10N/A
Commercial assay or kitMouse/rat IGF-1 Quantikine ELISA kitR and DR and D Systems, Inc, Minneapolis, MNN/A
Commercial assay or kitCorticosterone Competitive ELISA kitInvitrogenCat# EIACORTN/A
Commercial assay or kitiScript cDNA synthesis kitBIO-RADCat# 170–8891N/A
Commercial assay or kitSybr Green Master MixThermo FisherCat# A25778N/A
Commercial assay or kitSenescence detection kitAbcomCat#: AB65351N/A
AntibodyMac2
(rat monoclonal)
BioLegendCat# 125401
RRID:AB_1134237
IF(1:500)
IHC(1:500)
AntibodyPerilipin
(goat polyclonal)
NovusCat# NB100-60554
RRID:AB_922242
IF(1:500)
AntibodyInsulin
(guinea pig polyclonal)
DakoCat# A0564
RRID:AB_10013624
IF(1:500)
AntibodyGlucagon
(rabbit polyclonal)
InvitrogenCat# 15954–1-AP
RRID:AB_2878200
IF(1:500)
AntibodyAlexa Fluor 488 goat anti-guinea pig IgG (HCL)InvitrogenCat# A-11073
RRID:AB_2534117
IF(1:250)
AntibodyAlexa Fluor 594 donkey anti-rabbit IgG (HCL)InvitrogenCat# A32754
RRID:AB_2762827
IF(1:250)
AntibodyAlexa Fluor 594 donkey anti-goat IgG (HCL)InvitrogenCat# A32758
RRID:AB_2762828
IF(1:250)
AntibodyAlexa Fluor 488 goat anti-rat IgG (HCL)InvitrogenCat# A48262IF(1:250)
AntibodyCD45-PerCP/Cyanine5.5
(rat monoclonal)
BiolegendCat# 103132
RRID:AB_893340
FACS(1:400)
AntibodyCD11b-Pacific Blue
(rat monoclonal)
BiolegendCat# 101224
RRID:AB_755986
FACS(1:200)
AntibodyF4/80 -PE
(rat monoclonal)
BiolegendCat# 123110
RRID:AB_893486
FACS(1:200)
AntibodyCD11c -APC
(Armenian Hamster monoclonal)
BiolegendCat# 117310
RRID:AB_313779
FACS(1:200)
AntibodyCD206 -FITC
(rat monoclonal)
BiolegendCat# 141703
RRID:AB_10900988
FACS(1:200)
Sequence-based reagentGapdh _FThis paperPCR primersTGTGAACGGATTTGGCCGTA
Sequence-based reagentGapdh _RThis paperPCR primersACTGTGCCGTTGAATTTGCC
Sequence-based reagentF4/80_FThis paperPCR primersTGACTCACCTTGTGGTCCTAA
Sequence-based reagentF4/80_RThis paperPCR primersCTTCCCAGAATCCAGTCTTTCC
Sequence-based reagentIL-6_FThis paperPCR primersCCAGAGATACAAAGAAATGATGG
Sequence-based reagentIL-6_RThis paperPCR primersACTCCAGAAGACCAGAGGAAAT
Sequence-based reagentTNFα_FThis paperPCR primersGAGAAAGTCAACCTCCTCTCTG
Sequence-based reagentTNFα_RThis paperPCR primersGAAGACTCCTCCCAGGTATATG
Software, algorithmPrismGraphPad SoftwareGraphPad SoftwareN/A
Software, algorithmIllustratorAdobeN/AN/A
OtherKeyence BZ-X700 fluorescence microscopeKeyenceN/AN/A
OtherZeiss Axioskop FS2 microscopeZeissN/AN/A

Additional files

Source data 1

All raw datasets of each figure for this study.

https://cdn.elifesciences.org/articles/65108/elife-65108-data1-v2.xls
Supplementary file 1

Statistical information in each figure.

Table displaying the sample size, statistical test method, and p-value for the list figures.

https://cdn.elifesciences.org/articles/65108/elife-65108-supp1-v2.docx
Transparent reporting form
https://cdn.elifesciences.org/articles/65108/elife-65108-transrepform-v2.docx

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