Toll‑like receptor 2 mediates deposition of collagen I in adipose tissue of high fat diet‑induced obese mice

Obesity-induced secretory disorder of adipose tissue–derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)–infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow–specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.

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Increasing Dietary Fish Oil Reduces Adiposity and Mitigates Bone Deterioration in Growing C57BL/6 Mice Fed a High-Fat Diet

Journal of Nutrition ◽

10.1093/jn/nxz215 ◽

2019 ◽

Vol 150 (1) ◽

pp. 99-107 ◽

Cited By ~ 4

Author(s):

Jay J Cao ◽

Brian R Gregoire ◽

Kim G Michelsen ◽

Matthew J Picklo

Keyword(s):

Adipose Tissue ◽

Bone Mass ◽

Fish Oil ◽

High Fat Diet ◽

Bone Structure ◽

Tartrate Resistant Acid Phosphatase ◽

Serum Concentrations ◽

Obese Mice ◽

High Fat ◽

Long Chain

ABSTRACT Background Intake of total fat is linked to obesity and inversely associated with bone density in humans. Epidemiologic and animal studies show that long-chain n–3 (ω-3) PUFAs supplied as fish oil (FO) are beneficial to skeletal health. Objective This study tested the hypothesis that increasing dietary FO would decrease adiposity and improve bone-related outcomes in growing obese mice. Methods Male C57BL/6 mice at 6 wk old were assigned to 6 treatment groups and fed either a normal-fat diet (3.85 kcal/g and 10% energy as fat) or a high-fat diet (HF; 4.73 kcal/g and 45% energy as fat) containing either 0%, 3%, or 9% energy as FO (0FO, 3FO, and 9FO, respectively) ad libitum for 6 mo. Bone structure, body composition, and serum bone-related cytokines were measured. Results The HF diet increased the expression of the adipose tissue tumor necrosis factor α (Tnfa) and serum concentrations of leptin and tartrate-resistant acid phosphatase (TRAP), and decreased serum concentrations of osteocalcin and bone-specific alkaline phosphatase (P < 0.05). FO decreased fat mass (P < 0.05), serum TRAP (P < 0.05), and adipose tissue Tnfa expression (P < 0.01). Bone content of long-chain n–3 PUFAs was increased and n–6 PUFAs were decreased with the elevation in dietary FO content (P < 0.01). Compared with mice fed 9FO, animals fed 3FO had higher femoral bone volume/total volume (25%), trabecular number (23%), connectivity density (82%), and bone mass of second lumbar vertebrae (12%) and lower femoral trabecular separation (−19%). Mice fed the 3FO HF diet had 42% higher bone mass than those fed the 0FO HF diet. Conclusions These data indicate increasing dietary FO ≤3% energy can decrease adiposity and mitigate HF diet–induced bone deterioration in growing C57BL/6 mice possibly by reducing inflammation and bone resorption. FO at 9% diet energy had no further beneficial effects on bone of obese mice.

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Genistein inhibits high fat diet-induced obesity through miR-222 by targeting BTG2 and adipor1

Food & Function ◽

10.1039/c9fo00861f ◽

2020 ◽

Vol 11 (3) ◽

pp. 2418-2426 ◽

Cited By ~ 3

Author(s):

Mailin Gan ◽

Linyuan Shen ◽

Shujie Wang ◽

Zhixian Guo ◽

Ting Zheng ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

High Fat Diet ◽

Target Genes ◽

Obese Mice ◽

High Fat ◽

Diet Induced Obesity ◽

Regulate Lipid Metabolism

Genistein may regulate lipid metabolism in adipose tissue of obese mice by regulating the expression of miR-222 and its target genes, BTG2 and adipor1.

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Increased mitochondrial ROS generation mediates the loss of the anti-contractile effects of perivascular adipose tissue in high-fat diet obese mice

British Journal of Pharmacology ◽

10.1111/bph.13687 ◽

2017 ◽

Vol 174 (20) ◽

pp. 3527-3541 ◽

Cited By ~ 26

Author(s):

Rafael Menezes da Costa ◽

Rafael S Fais ◽

Carlos R P Dechandt ◽

Paulo Louzada-Junior ◽

Luciane C Alberici ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Ros Generation ◽

Obese Mice ◽

High Fat ◽

Perivascular Adipose Tissue ◽

Mitochondrial Ros

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Peripancreatic adipose tissue protects against high-fat-diet-induced hepatic steatosis and insulin resistance in mice

International Journal of Obesity ◽

10.1038/s41366-020-00657-6 ◽

2020 ◽

Vol 44 (11) ◽

pp. 2323-2334

Author(s):

Belén Chanclón ◽

Yanling Wu ◽

Milica Vujičić ◽

Marco Bauzá-Thorbrügge ◽

Elin Banke ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Insulin Levels ◽

Fat Depots ◽

Fat Depot

Abstract Background/objectives Visceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice. Subjects/methods Four adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4–5/group), cellular composition (FACS analysis, n = 5–6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6–10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5–11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8–10/group). Results We found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many “non-adipocytes” such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05). Conclusions PAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.

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