Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

AbstractProgranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.

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Abstract 023: Inducible Deletion of Adipocyte Prorenin Receptor Reverses Obesity Related Hypertension

Hypertension ◽

10.1161/hyp.70.suppl_1.023 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Eva Gatineau ◽

Dianne Cohn ◽

Ming Gong ◽

Frédérique Yiannikouris

Keyword(s):

Blood Pressure ◽

Adipose Tissue ◽

Lipid Metabolism ◽

Fat Mass ◽

High Fat Diet ◽

Standard Diet ◽

Mrna Levels ◽

High Fat ◽

Elevated Systolic Blood Pressure ◽

Prorenin Receptor

Obesity contributes to approximatively 2.5 million deaths every year and is associated with life threatening conditions including hypertension. Recently, we found that constitutive deletion of adipocyte (pro)renin-receptor (PRR) prevented high-fat diet-induced obesity through a drastic decrease in fat mass. However, adipocyte PRR deficient mice were characterized by a fatty liver and by an elevated systolic blood pressure (SBP), classic features of models of lipodystrophy. The purpose of this study was to investigate whether the temporally-controlled deletion of adipocyte PRR in obese mice reverses obesity related hypertension. After 18 weeks of high fat diet, inducible adipocyte-PRR deficient ( PRR ERT ) and control ( PRR fl/Y ) male mice (n=7-11 mice/ group) were injected intraperitoneally with tamoxifen (TMX) for 5 consecutive days. Body weight, body composition and blood pressure, measured by radiotelemetry in a subgroup of mice (n=2-4 mice/ group), were recorded before and after TMX injection. The inducible deletion of adipocyte PRR in PRR ERT mice decreased significantly body weights ( PRR fl/fl , 46.6 ± 1.3 g; PRR ERT , 42.1 ± 1.4 g, P<0.05) and fat mass ( PRR fl/fl , 15.8 ± 1.0 g; PRR ERT , 8.1 ± 0.7 g, P<0.05) compared to control mice. PPARγ, FABP4 and FAS mRNA levels were significantly decreased by 68% (6.8 out 10), 80% (8 out 10) and 68% (6.8 out 10) respectively in white adipose tissues of PRR ERT mice suggesting that PRR positively regulated adipogenesis and lipid metabolism in adipose tissue. In addition, the inducible deletion of adipocyte PRR in PRR ERT mice decreased significantly SBP compared to control mice ( PRR fl/fl , -4.3 ± 3.2 g; PRR ERT , -10.2 ± 2.4 g, P<0.05). Interestingly, adipocyte angiotensinogen mRNA abundance was significantly decreased in adipose tissue of PRR ERT mice fed a standard diet suggesting that the decrease in blood pressure might be mediated by a local renin angiotensin system (RAS). The measurement of local (liver, kidney, adipose tissue and brain) and systemic RAS in HF-fed mice is under investigation. Taken together, our results highlight a new signaling pathway in which PRR regulates adipogenesis, lipid metabolism and blood pressure. PRR could represent a new potential therapeutic target for obesity and hypertension.

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Gab2 deficiency suppresses high-fat diet-induced obesity by reducing adipose tissue inflammation and increasing brown adipose function in mice

Cell Death and Disease ◽

10.1038/s41419-021-03519-9 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Xinhui Wang ◽

Yinan Zhao ◽

Dekun Zhou ◽

Yingpu Tian ◽

Gensheng Feng ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Scaffolding Protein ◽

Regulation Mechanism ◽

Standard Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Relevant Regulation

AbstractObesity is caused by a long-term imbalance between energy intake and consumption and is regulated by multiple signals. This study investigated the effect of signaling scaffolding protein Gab2 on obesity and its relevant regulation mechanism. Gab2 knockout (KO) and wild-type (WT) mice were fed with a standard diet (SD) or high-fat diet (HFD) for 12 weeks. The results showed that the a high-fat diet-induced Gab2 expression in adipose tissues, but deletion of Gab2 attenuated weight gain and improved glucose tolerance in mice fed with a high-fat diet. White adipose tissue and systemic inflammations were reduced in HFD-fed Gab2 deficiency mice. Gab2 deficiency increased the expression of Ucp1 and other thermogenic genes in brown adipose tissue. Furthermore, the regulation of Gab2 on the mature differentiation and function of adipocytes was investigated in vitro using primary or immortalized brown preadipocytes. The expression of brown fat-selective genes was found to be elevated in differentiated adipocytes without Gab2. The mechanism of Gab2 regulating Ucp1 expression in brown adipocytes involved with its downstream PI3K (p85)-Akt-FoxO1 signaling pathway. Our research suggests that deletion of Gab2 suppresses diet-induced obesity by multiple pathways and Gab2 may be a novel therapeutic target for the treatment of obesity and associated complications.

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Glial A2B Adenosine Receptors Modulate Abnormal Tachykininergic Responses and Prevent Enteric Inflammation Associated with High Fat Diet-Induced Obesity

Cells ◽

10.3390/cells9051245 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1245 ◽

Cited By ~ 2

Author(s):

Vanessa D’Antongiovanni ◽

Laura Benvenuti ◽

Matteo Fornai ◽

Carolina Pellegrini ◽

Renè van den Wijngaard ◽

...

Keyword(s):

Glial Cell ◽

High Fat Diet ◽

Enzyme Linked Immunosorbent Assay ◽

Standard Diet ◽

Tlr4 Expression ◽

High Fat ◽

Toll Like Receptor 4 ◽

Diet Induced Obesity ◽

Adenosine A2b

The role played by adenosine A2B receptors (A2BRs) in the regulation of enteric glial cell (EGC) functions remains unclear. This study was aimed at investigating the involvement of A2BRs in the control of EGC functions in a model of obesity. C57BL/6 mice were fed with standard diet (SD) or high fat diet (HFD) for eight weeks. Colonic tachykininergic contractions were recorded in the presence of BAY60-6583 (A2BRs agonist), MRS1754 (A2BRs antagonist), and the gliotoxin fluorocitrate. Immunofluorescence distribution of HuC/D, S100β, and A2BRs was assessed in whole mount preparations of colonic myenteric plexus. To mimic HFD, EGCs were incubated in vitro with palmitate (PA) and lipopolysaccharide (LPS), in the absence or in the presence of A2BR ligands. Toll-like receptor 4 (TLR4) expression was assessed by Western blot analysis. Interleukin-1β (IL-1β), substance P (SP), and glial cell derived neurotrophic factor (GDNF) release were determined by enzyme-linked immunosorbent assay (ELISA) assays. MRS1754 enhanced electrically evoked tachykininergic contractions of colonic preparations from HFD mice. BAY60-6583 decreased the evoked tachykininergic contractions, with higher efficacy in HFD mice. Such effects were blunted upon incubation with fluorocitrate. In in vitro experiments on EGCs, PA and LPS increased TLR4 expression as well as IL-1β, GDNF, and SP release. Incubation with BAY60-6583 reduced TLR4 expression as well as IL-1β, GDNF, and SP release. Such effects were blunted by MRS1754. The present results suggest that A2BRs, expressed on EGCs, participate in the modulation of enteric inflammation and altered tachykininergic responses associated with obesity, thus representing a potential therapeutic target.

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SO023HEPATOCYTE GROWTH FACTOR (HGF) PRECLUDE HIGH-FAT DIET-INDUCED OBESITY AND IMPROVED INSULIN RESISTANCE IN MICE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa139.so023 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Jun Muratsu ◽

Yoshiaki Taniyama ◽

Fumihiro Sanada ◽

Atsuyuki Morishima ◽

Katsuhiko Sakaguchi ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

Growth Factor ◽

Inflammatory Mediators ◽

High Fat Diet ◽

Neutralizing Antibody ◽

Mrna Levels ◽

Wild Type ◽

High Fat

Abstract Background and Aims Obesity and its associated chronic inflammation in adipose tissue initiate insulin resistance, which is related to several pathologies including hypertension and atherosclerosis. Previous reports demonstrated that circulating hepatocyte growth factor (HGF) level was associated with obesity and type 2 diabetes. However, its precise role in obesity and related-pathology is unclear. Method In this experiment, cardiac-specific over-expression of human HGF in mice (HGF-Tg mice) which showed 4-5 times higher serum HGF levels than wild-type mice were used. We chose cardiac specific HGF overexpression, as other strain of HGF transgenic mice such as liver and kidney specific HGF overexpression mice develop cancer and cystic diseases, which are rare in the heart. In the present study, using HGF-Tg mice and anti-HGF neutralizing antibody (HGF-Ab), we explored the role of HGF in obese and insulin resistance induced by high fat diet (HFD) for 14 weeks (200 or 400ug/week). Results With normal chow diet (ND), there were no significant changes in body weight between WT and HGF-Tg mice. While body weight in wild-type mice fed with HFD for 14 weeks was significantly increased accompanied with insulin resistance, HGF-Tg mice prevented body weight gain and insulin resistance. Insulin resistance in obesity arises from the combination of altered functions of insulin target cells (e.g., liver, skeletal muscle, and adipose tissue) and the accumulation of macrophages that secrete pro-inflammatory mediators in adipose tissue. The accumulation of macrophages and elevated levels of inflammatory mediators in adipose tissue were significantly inhibited in HGF-Tg mice as compared to wild-type mice. In the gWAT, the mRNA levels of the mature macrophage marker F4/80, the chemoattractants, MCP-1 and CXCL2, and the inflammatory cytokines, such as TNF-α and iNOS, were significantly increased in WT mice fed with HFD. However, these levels were markedly reduced in HGF-Tg mice fed with HFD. Additionally, activation of Akt by insulin administration was significantly reduced in the gWAT SM, and liver by HFD; however, this activation was restored in HGF-Tg mice. Moreover, insulin-induced Akt signaling was decreased in HGF-Ab groups as compared to saline group under HFD condition. Importantly, HFD significantly increased the level of HGF mRNA by approximately 2 fold in gWAT, SM, and liver without changing cMet expression. All together, these data indicate that the HGF as one of the systemic gWAT, SM, and liver-derived growth factor plays a role in compensatory mechanism against insulin-resistance through the at least anti-inflammatory effect in adipose tissue. The HFD-induced obesity in wild-type mice treated with HGF-neutralizing antibody showed an exacerbated response to the glucose tolerance test. Conclusion HGF suppresses inflammation in adipose tissue induced by a high-fat diet, and as a result improves systemic insulin resistance. These gain-of-function and loss-of-function studies demonstrated that the elevated HGF level induced by HFD have protective role against obesity and insulin resistance.

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Developmental and nutritional changes of ob and PPARγ2 gene expression in rat white adipose tissue

Biochemical Journal ◽

10.1042/bj3210451 ◽

1997 ◽

Vol 321 (2) ◽

pp. 451-456 ◽

Cited By ~ 44

Author(s):

Véronique ROUSSEAU ◽

Dominique J. BECKER ◽

Lumbe N. ONGEMBA ◽

Jacques RAHIER ◽

Jean-Claude HENQUIN ◽

...

Keyword(s):

Adipose Tissue ◽

Cell Size ◽

White Adipose Tissue ◽

High Fat Diet ◽

Diet Composition ◽

Mrna Levels ◽

Fat Pad ◽

High Fat ◽

High Carbohydrate ◽

Fas Mrna

The ob gene encodes leptin, a hormone which induces satiety and increases energy expenditure. The peroxisome proliferator-activated receptor γ2 isoform (PPARγ2) gene encodes a transcription factor which controls adipocyte differentiation and expression of fat-specific genes. We have studied the regulation of these two genes in white adipose tissue (WAT) during the sucklingŐweaning transition. Suckling rats ingest a high-fat diet (milk). Fat-pad weight barely varied during the last week of suckling. ob mRNA levels, which were very low in 15-day-old rats, rose ∼ 6-fold until weaning at 21 days. When the rats were weaned on to a standard (high-carbohydrate) laboratory chow, epididymal WAT enlarged ∼ 7-fold, and ob mRNA kept increasing progressively and doubled between 21 and 30 days. This evolution contrasted with that of fatty acid synthase (FAS) mRNA, which increased sharply, but only after weaning. To distinguish between the influence of developmental and nutritional factors on ob expression, a group of rats was weaned on to a high-fat diet. This prevented the rise in glycaemia and insulinaemia and the decrease in plasma non-esterified fatty acids which otherwise occurred at weaning. This also resulted in a slight (10Ő15%) decrease in food intake and body weight gain. Under this high-fat diet, the rise of ob mRNA in WAT was augmented (3.7-fold in 30- versus 21-day-old pups), whereas the normal rise in FAS mRNA levels was attenuated. Fat-pad weights and adipocyte cell size and number were roughly similar in high-carbohydrate- and high-fat-weaned pups. mRNA levels of PPARγ2, like those of ob, were low in the WAT of 15-day-old suckling pups, doubled at 21 days, and reached a maximum as soon as 23 days. This evolution further differed from that of ob mRNA in not being influenced by diet composition. In conclusion, ob expression markedly increases during the sucklingŐweaning transition, and this effect is accentuated by a high-fat diet. Qualitative nutritional changes in ob mRNA were correlated with neither acute changes in adipose-tissue mass, nor cell size/number, nor variations in insulinaemia. PPARγ2 also increased during suckling, but rapidly reached a plateau after weaning and no longer changed thereafter. Unlike ob, PPARγ2 was not influenced by the diet composition.

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Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00798.2007 ◽

2008 ◽

Vol 294 (5) ◽

pp. E918-E927 ◽

Cited By ~ 113

Author(s):

David L. Allen ◽

Allison S. Cleary ◽

Kristin J. Speaker ◽

Sarah F. Lindsay ◽

Jill Uyenishi ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

High Fat Diet ◽

Growth Inhibitor ◽

Mrna Levels ◽

Wild Type ◽

Reporter Construct ◽

High Fat ◽

Visceral Adipose ◽

Activin Receptor Iib

Myostatin (MSTN) is a secreted growth inhibitor expressed in muscle and adipose. We sought to determine whether expression of MSTN, its receptor activin RIIb (ActRIIb), or its binding protein follistatin-like-3 (FSTL3) are altered in subcutaneous or visceral adipose or in skeletal muscle in response to obesity. MSTN and ActRIIb mRNA levels were low in subcutaneous (SQF) and visceral fat (VF) from wild-type mice but were 50- to 100-fold higher in both SQF and VF from ob/ob compared with wild-type mice. FSTL3 mRNA levels were increased in SQF but decreased in VF in ob/ob compared with wild-type mice. Moreover, MSTN mRNA levels were twofold greater in tibialis anterior (TA) from ob/ob mice, whereas ActRIIb and FSTL3 mRNA levels were unchanged. MSTN mRNA levels were also increased in TA and SQF from mice on a high-fat diet. Injection of ob/ob mice with recombinant leptin caused FSTL3 mRNA levels to decrease in both VF and SQF in ob/ob mice; MSTN and ActRIIb mRNA levels tended to decrease only in VF. Finally, MSTN mRNA levels and promoter activity were low in adipogenic 3T3-L1 cells, but an MSTN promoter-reporter construct was activated in 3T3-L1 cells by cotransfection with the adipogenic transcription factors SREBP-1c, C/EBPα, and PPARγ. These results demonstrate that expression of MSTN and its associated binding proteins can be modulated in adipose tissue and skeletal muscle by chronic obesity and suggest that alterations in their expression may contribute to the changes in growth and metabolism of lean and fat tissues occurring during obesity.

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Palmitoleic Acid (N-7) Attenuates the Immunometabolic Disturbances Caused by a High-Fat Diet Independently of PPARα

Mediators of Inflammation ◽

10.1155/2014/582197 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 26

Author(s):

Camila O. Souza ◽

Alexandre A. S. Teixeira ◽

Edson A. Lima ◽

Helena A. P. Batatinha ◽

Lara M. Gomes ◽

...

Keyword(s):

Insulin Resistance ◽

Oleic Acid ◽

High Fat Diet ◽

Palmitoleic Acid ◽

Serum Levels ◽

Standard Diet ◽

Liver Inflammation ◽

Wild Type ◽

High Fat

Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-αdependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF𝜅B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.

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Euterpe edulisExtract but Not Oil Enhances Antioxidant Defenses and Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/8173876 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Rodrigo Barros Freitas ◽

Rômulo Dias Novaes ◽

Reggiani Vilela Gonçalves ◽

Bianca Gazolla Mendonça ◽

Eliziária Cardoso Santos ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Antioxidant Defenses ◽

Standard Diet ◽

High Fat ◽

Nonalcoholic Fatty Liver

We investigated the effects ofE. edulisbioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in rats. All products were chemically analyzed.In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals’ diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacityin vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet-induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although bothE. edulisbioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins.

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The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages

Scientific Reports ◽

10.1038/s41598-021-98437-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wenyun Zeng ◽

Danbin Wu ◽

Yingxin Sun ◽

Yanrong Suo ◽

Qun Yu ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

High Fat Diet ◽

In Vitro Study ◽

Inflammasome Activation ◽

Mrna Levels ◽

High Fat ◽

Nlrp3 Inflammasome Activation ◽

Atherosclerosis Development

AbstractNLRP3 inflammasome is a vital player in macrophages pyroptosis, which is a type of proinflammatory cell-death and takes part in the pathogenesis of atherosclerosis. In this study, we used apoE−/− mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE−/− mice fed with high-fat diet for 12 weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48 h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root of apoE−/− mice. MCC950 inhibited the activation of NLRP3/ASC/Caspase-1/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1β and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.

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An ethanolic extract of Artemisia scoparia inhibits lipolysis in vivo and has antilipolytic effects on murine adipocytes in vitro

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00177.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. E1053-E1061 ◽

Cited By ~ 4

Author(s):

Anik Boudreau ◽

Allison J. Richard ◽

Jasmine A. Burrell ◽

William T. King ◽

Ruth Dunn ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Free Fatty Acid ◽

Microarray Analysis ◽

High Fat Diet ◽

Ethanolic Extract ◽

High Fat ◽

Artemisia Scoparia

An ethanolic extract of Artemisia scoparia (SCO) has metabolically favorable effects on adipocyte development and function in vitro and in vivo. In diet-induced obese mice, SCO supplementation significantly reduced fasting glucose and insulin levels. Given the importance of adipocyte lipolysis in metabolic health, we hypothesized that SCO modulates lipolysis in vitro and in vivo. Free fatty acids and glycerol were measured in the sera of mice fed a high-fat diet with or without SCO supplementation. In cultured 3T3-L1 adipocytes, the effects of SCO on lipolysis were assessed by measuring glycerol and free fatty acid release. Microarray analysis, qPCR, and immunoblotting were used to assess gene expression and protein abundance. We found that SCO supplementation of a high-fat diet in mice substantially reduces circulating glycerol and free fatty acid levels, and we observed a cell-autonomous effect of SCO to significantly attenuate tumor necrosis factor-α (TNFα)-induced lipolysis in cultured adipocytes. Although several prolipolytic and antilipolytic genes were identified by microarray analysis of subcutaneous and visceral adipose tissue from SCO-fed mice, regulation of these genes did not consistently correlate with SCO’s ability to reduce lipolytic metabolites in sera or cell culture media. However, in the presence of TNFα in cultured adipocytes, SCO induced antilipolytic changes in phosphorylation of hormone-sensitive lipase and perilipin. Together, these data suggest that the antilipolytic effects of SCO on adipose tissue play a role in the ability of this botanical extract to improve whole body metabolic parameters and support its use as a dietary supplement to promote metabolic resiliency.

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