Irving 2012 Abstract IOC72

From Bioblast
Irving BA (2012) AgRP deficient female mice have elevated body weight and hypothalamic mitochondrial oxidative capacity. Mitochondr Physiol Network 17.13.

Link: IOC72 Open Access

Irving BA (2012)

Event: IOC72

Brian Irving

The central orexigenic agouti-related protein (AgRP) increases food intake when ubiquitously over expressed. Unexpectedly, AgRP deficiency also produces elevated food intake in female, but not male AgRP (-/-) mice. Moreover, the female AgRP (-/-) tend to be heavier than their wild type (WT) littermates. We therefore examined whether differences in mitochondrial respiratory capacity and control could contribute to the propensity of the female AgRP (-/-) mice to eat more and gain more weight compared to their WT littermates. High-resolution respirometry was utilized to perform multiple substrate-inhibitor titration (SUIT) protocols designed to assess mitochondrial respiratory capacity and control in (mechanically and/or chemically) permeabilized hypothalamus, liver, skeletal muscle, and white adipose tissue acquired from female AgRP (-/-) and their WT littermates. In the hypothalamus, the female AgRP (-/-) mice had higher state-3 respiration (glutamate+malate+succinate+ADP) and higher maximally uncoupled respiration (FCCP) than their WT littermates. However, there were no significant differences between groups for the respiratory control ratios in the hypothalamus. Likewise, there were no significant differences between groups for the O2 fluxes or respiratory control ratios in the liver, white adipose tissue, or gastrocnemius muscle. Similar to the present results, obese Zucker rats were reported to have enhanced mitochondrial oxidative capacity in the hypothalamus (1). In conclusion, AgRP deficiency in female mice results in elevations in hypothalamic mitochondrial oxidative capacity, likely contributing to their increased food intake and body weight.

[1] Colombani AL, Carneiro L, Benani A, Galinier A, Jaillard T, Duparc T, Offer G, Lorsignol A, Magnan C, Casteilla L, Penicaud L, Leloup C (2009) Enhanced hypothalamic glucose sensing in obesity: alteration of redox signaling. Diabetes 58: 2189-2197 Open Access

β€’ Keywords: Orexins, Agouti-related protein, Obesity

β€’ O2k-Network Lab: US MN Rochester Nair KS, US PA Danville Irving BA, US LA Baton Rouge Irving BA

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression, Exercise physiology;nutrition;life style  Pathology: Obesity 

Organism: Mouse, Rat  Tissue;cell: Skeletal muscle, Nervous system, Liver, Fat  Preparation: Permeabilized tissue 

Coupling state: OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k, TIP2k 

Affiliations and author contributions

Brian Irving (1,2), Steve Roesch (2), Crystal Kane (1,2), Amanda Styer (2), George Argyropoulos (1,2)

(1) Geisinger Obesity Institute; Email: [email protected]

(2) Weis Center for Research, Geisinger Medical Center, Danville, PA


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