Title : Positive adipose liver crosstalk protects adipose MTP knockout Mice from hepatic steatosis on an obesogenic diet.
Introduction: Our previous study demonstrated that adipocyte MTP regulates intracellular lipolysis by inhibiting ATGL activity. Adipose-specific MTP knockout mice (A-Mttp-/-) had smaller adipocytes and showed increased thermogenesis, and gained less weight on an obesogenic diet. They also exhibited moderately high plasma triglyceride levels and less hepatic steatosis compared to wild-type counterparts. In this study, we have elucidated the mechanism behind less haptic lipid accumulation and moderately high plasma TG in A-Mttp-/- mice.
Methods: We characterized lipoproteins using FPLC and studied hepatic ApoB production. We have analyzed adipose-liver crosstalk using two strategies 1) by performing lipidomics of adipose tissue, plasma, and liver. 2) Adipokine profiling of A-Mttp-/- and Mttpf/f mice plasma. Further, we have used western blotting and qRT-PCR to check signaling and gene expression.
Results: Plasma lipid profiling revealed increased TG content in the VLDL and LDL fraction of A-Mttp-/- mice compared to Mttpf/f mice. Additionally, A-Mttp-/- mice showed significantly increased hepatic triglyceride production compared to the wild type. Lipidomic analysis revealed the movement of fatty acids from adipose tissue to the liver, resulting in significantly higher amounts of oleate, palmitate, linoleate, and stearate in the liver of A-Mttp-/- mice compared to Mttpf/f mice. A-Mttp-/- mice liver also showed significantly increased expression of genes involved in fatty acid uptake and utilization such as Cd36, Mcad, Fatp2, and Cpt1a compared to Mttpf/f mice. Further adipokine profiling showed a significantly higher amount of adiponectin and decreased amount of proinflammatory cytokines such as leptin in the plasma of A-Mttp-/- mice compared to Mttpf/f mice. We also found decreased ceramide levels and significantly increased phosphorylation of AMPK in the liver of A-Mttp-/- mice compared to Mttpf/f mice.
Conclusion: We conclude that increased availability of substrate for TG production might contribute to increased ApoB secretion by the liver of A-Mttp-/- mice. In addition, positive cytokine profile in these mice may protect A-Mttp-/- mice from hepatic steatosis. Our study highlights the significance of adipokines and the movement of FFA from adipose tissue to the liver as essential for maintaining a healthy liver.
What will audience learn from your presentation?
Audience will learn how adipose tissue regulates liver triglyceride secretion and helps in maintaining healthy liver. Researchers attending the conference could further expand the study and discover new therapeutic targets for diabetes and its related complications.