Randall H. Friedline

Increased Insulin Action, Glucose Metabolism and Muscle Function in Supervillin‐Knockout and Supervillin‐Mutant Mice

Tara C. Smith, LAUREN A. TAUER, Randall H. Friedline, Xiaodi Hu et autres

We here describe mouse models with complementary homozygous Svil mutations. In skeletal muscle, Svil-Mut mice express the Svil-encoded N-terminus fused to the βgal-neo gene-trap tag and lack the highly conserved archvillin C-terminus; Svil-KO mice lack expression of all known Svil-encoded proteins; and …

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Author Correction: IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease

Randall H. Friedline, Hye Lim Noh, Sujin Suk, Mahaa Albusharif et autres

The original version of this Article contained an error in the methods, which read “RNA-seq data analysis of TILAM in human subjects with MASLD and MASH”. The correct version now states “RNA-seq data analysis of liver genes in human subjects with MASLD …

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IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease

Randall H. Friedline, Hye Lim Noh, Sujin Suk, Mahaa Albusharif et autres

Abstract Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ …

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Crosstalk between corepressor NRIP1 and cAMP signaling on adipocyte thermogenic programming

Emmanouela Tsagkaraki, Adı́lson Guilherme, Sarah M. Nicoloro, Mark Kelly et autres

OBJECTIVES: Nuclear receptor interacting protein 1 (NRIP1) suppresses energy expenditure via repression of nuclear receptors, and its depletion markedly elevates uncoupled respiration in mouse and human adipocytes. We tested whether NRIP1 deficient adipocytes implanted into obese mice would enhance whole body metabolism. …

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An insulin-regulated arrestin domain protein controls hepatic glucagon action

Sezin Dağdeviren, Megan F. Hoang, Mohsen Sarikhani, Vanessa Meier et autres

Glucagon signaling is essential for maintaining normoglycemia in mammals. The arrestin fold superfamily of proteins controls the trafficking, turnover, and signaling of transmembrane receptors as well as other intracellular signaling functions. Further investigation is needed to understand the in vivo functions of …

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293-OR: Macrophage-Derived Interleukin-12 Regulates Obesity-Mediated Insulin Resistance in the Liver

Randall H. Friedline, Mahaa Albusharif, ALLISON M. KIM, LAUREN H. KIM et autres

Inflammation and insulin resistance play a major role in nonalcoholic fatty liver disease (NAFLD), and IL-12, a pro-inflammatory cytokine primarily secreted by macrophages, is elevated in obesity. Here, we examined the effects of acute treatment with IL-12 in vivo on glucose metabolism …

Hepatic Phospholipid Remodeling Modulates Insulin Sensitivity and Systemic Metabolism

Ye Tian, Kritika Mehta, Matthew J. Jellinek, Hao Sun et autres

The liver plays a central role in regulating glucose and lipid metabolism. Aberrant insulin action in the liver is a major driver of selective insulin resistance, in which insulin fails to suppress glucose production but continues to activate lipogenesis in the liver, …

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A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis

Qingbo Chen, Lei Huang, Dongning Pan, Kai Hu et autres

The signaling mechanisms underlying adipose thermogenesis have not been fully elucidated. Particularly, the involvement of adipokines that are selectively expressed in brown adipose tissue (BAT) and beige adipocytes remains to be investigated. Here we show that a previously uncharacterized adipokine (UPF0687 protein …

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Differential effects of Akkermansia-enriched fecal microbiota transplant on energy balance in female mice on high-fat diet

Kalpana D. Acharya, Randall H. Friedline, Doyle V. Ward, Madeline Graham et autres

Estrogens protect against weight gain and metabolic disruption in women and female rodents. Aberrations in the gut microbiota composition are linked to obesity and metabolic disorders. Furthermore, estrogen-mediated protection against diet-induced metabolic disruption is associated with modifications in gut microbiota. In this …

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Paradoxical activation of transcription factor SREBP1c and de novo lipogenesis by hepatocyte-selective ATP-citrate lyase depletion in obese mice

Batuhan Yenilmez, Mark Kelly, Guofang Zhang, Nicole Wetoska et autres

Hepatic steatosis associated with high-fat diet, obesity, and type 2 diabetes is thought to be the major driver of severe liver inflammation, fibrosis, and cirrhosis. Cytosolic acetyl CoA (AcCoA), a central metabolite and substrate for de novo lipogenesis (DNL), is produced from …

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270-OR: Loss of Myeloid IFNgamma Signaling Prevents Hepatic Inflammation and NASH in Obesity

Randall H. Friedline, Mahaa Albusharif, Hye Lim Noh, ALLISON M. KIM et autres

Nonalcoholic steatohepatitis (NASH) is a major complication of obesity, and interferon-γ (IFNγ) is a key regulator of innate and adaptive immunity by priming macrophages and inducing an inflammatory response. We have recently generated mice with conditional deletion of IFNγ receptor in myeloid …

Paradoxical activation of SREBP1c and de novo lipogenesis by hepatocyte-selective ACLY depletion in obese mice

Batuhan Yenilmez, Mark Kelly, Guofang Zhang, Nicole Wetoska et autres

ABSTRACT Hepatic steatosis associated with high fat diets, obesity and type 2 diabetes is thought to be the major driver of severe liver inflammation, fibrosis, and cirrhosis. Cytosolic acetyl-coenzyme A (AcCoA), a central metabolite and substrate for de novo lipogenesis (DNL), is …

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