Metabolically distinct weight loss by 10,12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice

Abstract

BackgroundWidely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance.ObjectiveWe therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15–25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism.MethodsObese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss. Metabolic endpoints such as energy expenditure, glucose and insulin tolerance testing, and trunk fat distribution were measured.ResultsBy design, 10,12 CLA and CR caused equivalent weight loss, with greater fat loss by 10,12 CLA accompanied by increased energy expenditure, reduced respiratory quotient, increased fat oxidation, accumulation of alternatively activated macrophages, and browning of subcutaneous white adipose tissue (WAT). Moreover, 10,12 CLA-supplemented mice better defended their body temperature against a cold challenge. However, 10,12 CLA concurrently induced the detrimental loss of subcutaneous WAT without reducing visceral WAT, promoted reduced plasma and WAT adipokine levels, worsened hepatic steatosis, and failed to improve glucose metabolism. Obese mice undergoing CR were protected from subcutaneous-specific fat loss, had improved hepatic steatosis, and subsequently showed the expected improvements in WAT adipokines, glucose metabolism and WAT inflammation.ConclusionsThese results suggest that 10,12 CLA mediates the preferential loss of subcutaneous fat that likely contributes to hepatic steatosis and maintained insulin resistance, despite significant weight loss and WAT browning in mice. Collectively, we have shown that weight loss due to 10,12 CLA supplementation or CR results in dramatically different metabolic phenotypes, with the latter promoting a healthier form of weight loss.

Lithocholic Acid Improves the Survival of Drosophila Melanogaster

“…Although LCA‐treated flies experienced a significant extension of their lifespans, they also registered higher glucose levels (Figure c) while the triglyceride (Figure SF1a, Supporting Information) and protein (Figure SF1b, Supporting Information) levels remained unchanged. This observation is in contrast to findings from other reports showing that lower glucose levels are associated with lifespan extension . Indeed, Schulz and co‐workers have demonstrated an extended lifespan in glucose‐restricted C. elegans depending on the activated AAK‐2, the mammalian AMPK ortholog.…”

Chronic oral rapamycin decreases adiposity, hepatic triglycerides and insulin resistance in male mice fed a diet high in sucrose and saturated fat

“…Intraperitoneal glucose (1 mg kg −1 ) and insulin (0.75 U kg −1 ) tolerance tests were performed after a 4 h fast as described previously (Subramanian et al, 2008). Body composition was measured non-invasively in conscious immobilized mice (n = 7-8 mice per group) using quantitative magnetic resonance (EchoMRI whole body composition analyser; Echo Medical Systems, Houston, TX, USA) by the University of Washington Nutrition Obesity Research Center Energy Balance Core, as described previously (den Hartigh et al, 2017). All analyses were performed in a blinded manner.…”

10,12 Conjugated Linoleic Acid-Driven Weight Loss Is Protective against Atherosclerosis in Mice and Is Associated with Alternative Macrophage Enrichment in Perivascular Adipose Tissue

“…As such, CLA supplement users ingest significantly more 10,12 CLA than would be obtained from the diet. Supplemental CLA promotes significant weight loss in animals and modest weight loss in humans, an effect now attributed to the 10,12 CLA isomer [ 4 ]. We have previously shown that 10,12 CLA reduces lipid accumulation by increasing fatty acid oxidation in a cell line derived from (mouse) 3T3 cells (3T3-L1) adipocytes [ 5 ].…”

“…We have previously shown that 10,12 CLA reduces lipid accumulation by increasing fatty acid oxidation in a cell line derived from (mouse) 3T3 cells (3T3-L1) adipocytes [ 5 ]. Moreover, obese mice supplemented with 10,12 CLA lose body weight and fat mass due to enhanced fatty acid oxidation with increased energy expenditure and white adipose tissue browning [ 4 ]. These changes in energy expenditure are not the result of weight loss per se, as a control group undergoing caloric restriction to mirror weight loss by the 10,12 CLA-supplemented group did not exhibit these changes [ 4 ].…”