Abstract
Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.
Highlights
The transition period is the most metabolically challenging period for dairy cattle and is characterized by homeostatic changes, negative energy balance (NEB), and increased risk for metabolic disorders [1, 2]
Nine replicate samples were used for each condition (N = 9). (A–C) The mRNA expression levels of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). (D–F) Supernatant concentrations of IL-1β, IL-6, and TNF-α. (C) Control group
Adipose tissue is simple lipid storage, and an endocrine tissue, which can participate in the synthesis and secretion of inflammatory cytokines, including IL-1β, IL-6, and TNF-α [26]
Summary
The transition period is the most metabolically challenging period for dairy cattle and is characterized by homeostatic changes, negative energy balance (NEB), and increased risk for metabolic disorders [1, 2]. Over 60% of all dairy cows develop ketosis or fatty liver during the transition period, which is a direct response to an energy imbalance and may decrease hepatic efficiency, animal health, and milk production [3, 4]. The lipid metabolism of adipose tissue in cows with ketosis or fatty liver exhibited a disordered state. Lipid droplets (LDs) are monolayer organelles in the cytoplasm of adipocytes and are shown to be highly dynamic, playing a key role in maintaining energy homeostasis [7]. Perilipin 1 (PLIN1) is highly expressed in white adipocytes and is actively involved in the regulation of lipolysis through interaction with lipases [hormonesensitive lipase (HSL)] and lipase activators [CGI-58 for adipose triglyceride lipase (ATGL)] [10, 11]. The relevant mechanism of PLIN1 on the lipid metabolism of adipocytes is still not completely characterized
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