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BMAL1 is a core component of the transcription/translation machinery that regulates central and peripheral circadian rhythms that coordinate behavior and metabolism, respectively. Our objective was to determine the impact of BMAL1 in adipose alone or in combination with liver on metabolic phenotypes. Control, adipose-Bmal1 knockout (ABKO), and liver- and adipose- Bmal1 knockout (LABKO) female mice were placed in TSE System metabolic chambers for metabolic phenotyping. A second cohort of male mice was fed a control or diabetogenic diet, and body weight and composition, glucose tolerance, insulin sensitivity, and serum and hepatic lipids were measured. Both female ABKO and LABKO mice exhibited increased food consumption compared with control mice. ABKO mice also exhibited increased overall activity predominantly during the light phase compared with both control and LABKO mice and were protected from increased weight gain. When the male cohort was challenged with a diabetogenic diet, LABKO mice had increased body weight due to increased fat mass compared with control and ABKO mice. However, these mice did not present further impairments in glycemic control, adipose inflammation, or liver injury. LABKO mice had increased hepatic cholesterol and elevated expression of cholesterol synthesis and uptake genes. Our data indicate that deletion of this allele in adipose or in combination with liver alters feeding behavior and locomotor activity. However, obesity is exacerbated only with the combination of liver and adipose deletion. [ABSTRACT FROM AUTHOR]

ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER. [ABSTRACT FROM AUTHOR]