• Title Emeritus Professor
  • Education PhD: Purdue University
  • Office K603
  • Phone 617-358-4579
  • Area of Interest Cell biology of adipocytes

Fat cells or adipocytes play a key role in the regulation of metabolism by insulin and other hormones. Obesity, too much fat, can lead to insulin resistance, diabetes and other pathologies due to failure of these cells to adequately store fat and its subsequent harmful spillover to other tissues. Surprisingly, a severe lack of fat in rare instances of genetic lipodystrophy causes similar problems. Moreover, there are “healthy obese” individuals who are able to accommodate an overabundance of fat without developing insulin resistance and diabetes. Our goals are to determine the mechanism(s) of fat cell dysfunction in both obesity/diabetes and lipodystrophy, which may eventually show the way to treatments and cures.

An interesting morphological feature of adipocytes is the unusually high number of plasma membrane micro-domains called caveolae, invaginations resembling little caves, which comprise 50% of their cell surface. We have engineered mice to lack a protein component of caveolae, cavin-1, called Polymerase 1 Transcription Releasing Factor (PTRF) which leads to a total loss of caveolae in in all tissues and results in profound insulin resistance and lipodystrophy (1,2), pathologies identical to those resulting from functional loss of cavin-1/PTRF in humans. The dysfunctional adipocytes in this condition result in large part from the absence of PTRF and subsequent inadequate ribosomal adaption such that the fat cells cannot respond to normal fasting and feeding cycles and lose protein mass and the ability to adequately store fat (3).

Adipose tissue is a robust endocrine organ that makes and secretes hormone-like proteins called adipokines, which have profound affects on insulin sensitivity (adiponectin) and energy balance (leptin) to name 2 examples. We have identified in the adipocyte endoplasmic reticulum (E.R.), adiporedoxin (Adrx), an oxidoreductase that is most highly expressed in fat cells. Adrx loss and over expression cause decreases and increases in the secretion of various proteins including adiponectin and collagens (4). Diminished collagen secretion in the Adrx null mouse reduces adipocyte fibrosis and would be expected to enhance fat cell adaptability. On the other hand, reduced adiponectin secretion should be deleterious to metabolic regulation. We are sorting out these details in mice and adipocyte cell lines.

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