DOI: 10.7488/ds/7809
title: Dataset: Adiponectin influences the effects of caloric restriction on liver function, skeletal muscle, and systemic metabolic homeostasis _v2024_09_19

description: This dataset contains data for a manuscript that is being submitted for publication in September 2024. Once published, this dataset will be updated with the DOI for the manuscript. The Abstract for the current version of the manuscript is as follows: Adiponectin is the most-abundant hormone in the circulation. Despite being secreted almost exclusively by adipocytes, circulating adiponectin decreases in obesity and insulin resistance but increases in lean states, including caloric restriction (CR) in animals and humans. Preclinical studies suggest that, in obesity and other adverse contexts, adiponectin deficiency promotes cardiometabolic dysfunction whereas increasing adiponectin improves cardiometabolic health. However, the fundamental roles of adiponectin in physiological, evolutionarily relevant contexts, including hyperadiponectinaemia during CR, have been largely overlooked. We hypothesised that increased adiponectin contributes to the metabolic benefits of CR, including greater glucose tolerance and fat oxidation. To test this, we investigated the effect of global adiponectin knockout (KO) in male and female mice fed ad libitum (AL) or 30% CR from 9-13 weeks of age. Adiponectin KO did not alter CR’s effects on body mass or composition but, unexpectedly, enhanced CR’s ability to improve glucose tolerance. This occurred without altering insulin sensitivity or secretion and instead was driven by fasting hypoglycaemia in KO mice during CR. Adiponectin KO also augmented CR-induced increases in plasma fatty acids but did not alter systemic lipid oxidation in either sex. Hepatic triglycerides and sphingolipids were also unaffected by adiponectin deficiency; however, RNAseq revealed that, during CR, KO compromised hepatic gluconeogenesis in males and promoted hepatic amino acid catabolism in both sexes. This occurred without sarcopenia or elevated protein catabolism in skeletal muscle. Instead, RNAseq indicated that adiponectin KO impaired mitochondrial metabolism and stimulated immunological activity in skeletal muscle of CR males, while CR females’ muscle was largely unaffected. Our study is the first to investigate the role of adiponectin in CR’s metabolic effects. Together, our findings suggest that, in both sexes, adiponectin evolved to help maintain blood glucose during prolonged fasting and that variation in adiponectin influences CR’s metabolic benefits. We contend that the widely reported functions of adiponectin in pathological contexts, such as obesity and insulin resistance, differ substantially to its roles during CR and other physiological conditions in which circulating adiponectin is increased. For further details please see the file named "Readme metadata file"
description: 1. Adiponectin_KO_CR_Paper_Source_Data_all_figures_v2024_09_11.xlsx This Excel file contains the source data for the figures presented in the manuscript submitted for publication in September 2024. It contains the following 83 worksheets, each of which consists of the data used to generate figures. It can be read as a csv file. Note that any abbreviations are defined in each worksheet: 1. The sheet named "Figures 1A" contains data from plasma adiponectin concentrations from male and female WT mice from 9-15 weeks of age 2. The sheet named "Figure 1B-C, S1A-B" contains data for body mass, fat mass and lean mass of wild-type (WT) and adiponectin knockout (KO) males and females fed ad libitum (AL) or 30% calorie restricted diet (CR) from 9-13 weeks of age 3. The sheet named "Figure 1D-E, S1C-D, S5A-B" and "Figure S12A-D" contains data for tissue masses of WT and adiponectin KO males and females fed AL or CR from 9-13 weeks of age. The masses were recorded at necropsy (13-week-old mice). 4. The sheets named "Figure 2A", "Figure 2B", "Figure 2C", "Figure 2D", "Figure 2E", "Figure 2E", "Figure S3A", and "Figure S3B" contain data from oral glucose tolerance test (OGTT) of WT and adiponectin KO males and females fed AL or CR for 3.5 weeks. 5. The sheets named "Figure S3C" and "Figure S3D" contain data from Insulin tolerance test (ITT) of WT and adiponectin KO males and females fed AL or CR for 3 weeks. 6. The sheet named "Figure 3A" contains data from plasma NEFA concentrations of WT and adiponectin KO males and females fed AL or CR for 4 weeks. 7. The sheets named "Figure 3B", "Figure 3C", "Figure 3D", "Figure 3E", and "Figure 3F" contain data from Oral lipid tolerance test (OLTT) of WT and adiponectin KO males and females fed AL or CR for 3.5 weeks. 8. The sheets named "Figure 4A", "Figure 4B", "Figure 4CDEF", "Figure S4A", " Figure S4B", "Figure S4CD", and "Figure S4EF"contain data from indirect calorimetry of WT and adiponectin KO males and females fed AL or CR for 2.5 weeks. 9. The sheets named "Figure 5A, S7C, S10A_M_AL_KO&gt;WT ", " Figure 5A, S7C, S10A_M_AL_KOWT ", " Figure 5A, S7C, S10A, M_CR_KOWT", "Fig S7C, S8A, S10C F_AL_KOWT", "Fig S7C, S8A, S10C F_CR_KOWT ", " Figure 6A, S14C, S17A_M_AL_KOWT ", " Figure 6A, S14C, S17A_M_CR_KOWT ", "Fig S14C, S16A, S17C_F_AL_WT&gt;KO", "Fig S14C, S16A, S17C_F_CR_KO&gt;WT", "Fig S14C, S16A, S17C_F_CR_WT&gt;KO", "Figure S15A", "Figure S15B", "Figure S16B", "Figure S16C", "Figure S17D", "Figure S18A", "Figure S18B", "Figure S18C", "Figure S19C", "Figure S20A", Relationship between files, if important: File 1 contains sheets of summary data, including raw data and calculations used to generate the final data File 2 is this readme file.