The effect of diet on thermogenesis in acquired lipodystrophy

Robbins, David C.; Danforth, Elliot; Horton, Edward S.; Burse, Richard L.; Goldman, Rachel; Sims, Ethan A. H.

doi:10.1016/0026-0495(79)90090-8

Cited by 39 publications

(25 citation statements)

References 17 publications

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“…Confirmation of apoptosis was obtained by demonstrating an increase in caspase activity in the cells. For both the dose and time course experiments, the concentrations of pioglitazone were consistent with in vivo plasma levels after administration of pioglitazone (14). LPS, a known endotoxin that is the major structural component of the outer wall of Gram-negative bacteria, is a potent activator of macrophage cytokine production and was used to activate THP1 cells, and treatment with LPS followed by pioglitazone showed an increased tendency of cells to undergo apoptosis.…”

Section: Discussionsupporting

confidence: 61%

“…TPA was applied to the cells upon plating in order to stimulate their differentiation into macrophage-like cells. This treatment was continued for 4 days to ensure that nearly 100% of the cells underwent macrophage differentiation (14). Further treatment with LPS resulted in activation and stimulation of these macrophage-like cells.…”

Section: Pioglitazone Acts Directly On Macrophagesmentioning

confidence: 99%

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Pioglitazone induces apoptosis of macrophages in human adipose tissue

Bodles

Varma

Yao-Borengasser

et al. 2006

Journal of Lipid Research

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Metabolic syndrome and type 2 diabetes mellitus are associated with an increased number of macrophage cells that infiltrate white adipose tissue (WAT). Previously, we demonstrated that the treatment of subjects with impaired glucose tolerance (IGT) with the peroxisome proliferatoractivated receptor g (PPARg) agonist pioglitazone resulted in a decrease in macrophage number in adipose tissue. Here, adipose tissue samples from IGT subjects treated with pioglitazone were examined for apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. TUNEL-positive cells were identified, and there was a significant 42% increase in TUNELpositive cells following pioglitazone treatment. Overlay experiments with anti-CD68 antibody demonstrated that most of the TUNEL-positive cells were macrophages. To determine whether macrophage apoptosis was a direct or indirect effect of pioglitazone treatment, human THP1 cells were treated with pioglitazone in vitro, demonstrating increased TUNEL staining in a dose-and time-dependent manner. Furthermore, the appearance of the active proteolytic subunits of caspase-3 and caspase-9 were detected in cell lysate from THP1 cells and also increased in a dose-and time-dependent manner following pioglitazone treatment. Pretreatment with a PPARg inhibitor, GW9662, prevented pioglitazone induction of the apoptotic pathway in THP1 cells. Differentiated human adipocytes did not show any significant increase in apoptosis after treatment in vitro with piolgitazone. These findings indicate that PPARg has distinct functions in different cell types in WAT, such that pioglitazone reduces macrophage infiltration by inducing apoptotic cell death specifically in macrophages through PPARg activation.-Bodles, A. M., V.

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Section: Discussionsupporting

confidence: 61%

Section: Pioglitazone Acts Directly On Macrophagesmentioning

confidence: 99%

Pioglitazone induces apoptosis of macrophages in human adipose tissue

Bodles

Varma

Yao-Borengasser

et al. 2006

Journal of Lipid Research

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“…One of the most effective and important components of management of lipodystrophy is caloric restriction, in order to minimise the stress imparted on limited or absent fat depots that are already sick and failing (Robbins et al 1979). The low levels of leptin production worsen the situation by precipitating hyperphagia, which is often extreme.…”

Section: Adipose Tissue As a Key Mediator Of Metabolic Healthmentioning

confidence: 99%

Lipodystrophy: metabolic insights from a rare disorder

Huang-Doran¹,

Sleigh²,

Rochford³

et al. 2010

Journal of Endocrinology

176

147

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Obesity, insulin resistance and their attendant complications are among the leading causes of morbidity and premature mortality today, yet we are only in the early stages of understanding the molecular pathogenesis of these aberrant phenotypes. A powerful approach has been the study of rare patients with monogenic syndromes that manifest as extreme phenotypes. For example, there are striking similarities between the biochemical and clinical profiles of individuals with excess fat (obesity) and those with an abnormal paucity of fat (lipodystrophy), including severe insulin resistance, dyslipidaemia, hepatic steatosis and features of hyperandrogenism. Rare lipodystrophy patients therefore provide a tractable genetically defined model for the study of a prevalent human disease phenotype. Indeed, as we review herein, detailed study of these syndromes is beginning to yield valuable insights into the molecular genetics underlying different forms of lipodystrophy, the essential components of normal adipose tissue development and the mechanisms by which disturbances in adipose tissue function can lead to almost all the features of the metabolic syndrome.

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“…Insulin and insulin secretagogues and dietary restriction (9) are only partially effective. Modest success has been achieved with insulin-sensitizing agents, the thiazolidinediones (5,10,11) and metformin (12).…”

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confidence: 99%

WY14,643, a Peroxisome Proliferator-activated Receptor α (PPARα) Agonist, Improves Hepatic and Muscle Steatosis and Reverses Insulin Resistance in Lipoatrophic A-ZIP/F-1 Mice

Chou¹,

Haluzı́k²,

Gregory³

et al. 2002

Journal of Biological Chemistry

180

132

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WY14,643 is a specific peroxisome proliferator-activated receptor ␣ (PPAR␣) agonist with strong hypolipidemic effects. Here we have examined the effect of WY14,643 in the A-ZIP/F-1 mouse, a model of severe lipoatrophic diabetes. With 1 week of treatment, all doses of WY14,643 that were tested normalized serum triglyceride and fatty acid levels. Glucose and insulin levels also improved but only with high doses and longer treatment duration. WY14,643 reduced liver and muscle triglyceride content and increased levels of mRNA encoding fatty acid oxidation enzymes. In liver, the elevated lipogenic mRNA profile (including PPAR␥) in A-ZIP/F-1 mice remained unchanged. These results suggest that WY14,643 acts by increasing ␤-oxidation rather by than decreasing lipogenesis or lipid uptake. Hyperinsulinemic euglycemic clamp studies indicated that WY14,643 treatment improved liver more than muscle insulin sensitivity and that hepatic mRNA levels of gluconeogenic enzymes were reduced. Combination treatment with both WY14,643 and a PPAR␥ ligand, rosiglitazone, did not lower glucose levels more effectively than did treatment with WY14,643 alone. These data support the hypothesis that reducing intracellular triglycerides in non-adipose tissues improves insulin sensitivity and suggest that further investigation of the role of PPAR␣ agonists in the treatment of lipoatrophic diabetes is warranted.

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The effect of diet on thermogenesis in acquired lipodystrophy

Cited by 39 publications

References 17 publications

Pioglitazone induces apoptosis of macrophages in human adipose tissue

Pioglitazone induces apoptosis of macrophages in human adipose tissue

Lipodystrophy: metabolic insights from a rare disorder

WY14,643, a Peroxisome Proliferator-activated Receptor α (PPARα) Agonist, Improves Hepatic and Muscle Steatosis and Reverses Insulin Resistance in Lipoatrophic A-ZIP/F-1 Mice

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