A Remembrance and Obituary
Written by: Harvey Grill and Allen Levine
Tim Bartness died on September 24, 2015 in Atlanta, GA. at the age of 62 after battling multiple myeloma for the past year. His impact on obesity research and on his fellow scientists is worthy of attention. Tim’s interests were broad and he contributed insightfully and deeply to our knowledge of adipose tissue (white [WAT] and brown [BAT]) and its sympathetic and sensory nervous system innervation, the neural control of WAT lipolysis and BAT thermogenesis, obesity reversal, the neural control of foraging and hoarding, and photoperiodism/melatonin receptor signaling. Tim was a sought after and extremely effective speaker at many international meetings related to the neural control of adipose tissue, obesity and ingestive behavior. His work is widely cited and has significantly advanced our understanding of and appreciation for the functional effects subserved by the brain-adipose and adipose-brain axes.
Tim’s major scientific contributions include a theme he pursued as a postdoctoral fellow that continued in the lab he established at Georgia State University. Early in his career he identified the mechanisms mediating how seasonal changes in the photoperiod reversed the naturally occurring obesity of Siberian hamsters (from 50% to 20 % body fat). This work was particularly relevant, because it began when the human obesity epidemic was just being recognized as a disease of enormous proportions. He demonstrated that it is the duration of nocturnal melatonin secretion that faithfully encodes day length (photoperiod) cues and causes seasonal obesity through modulating the activity of the central sites of sympathetic nervous system (SNS) outflow to WAT.
Through work with this model, using then novel transneuronal viral tract tracing methods, Tim was the first to reveal the pre- and post-ganglionic sympathetic innervation of WAT. This method enables the identification of a functionally connected neuronal circuit and was the first demonstration of the CNS origins of the SNS outflow from brain to WAT. Importantly soon after his lab also described the CNS origins of the SNS efferent pathways innervating brown adipose tissue (BAT).
Having defined the CNS sources of SNS outflow to WAT he returned to the photoperiod work and complemented his previous findings by demonstrating that melatonin receptor mRNA is co-localized with these CNS SNS outflow neurons. His group also demonstrated that changes in the photoperiod activated these circuits and increased the sympathetic drive (norepinephrine turnover) to adipose tissue via ß-adrenergic receptors on white adipocytes. By combining PRV tract tracing with in situ hybridization, he (Denis Richard and collaborators) identified key neurotransmitter systems involved in sympathetic outflow to WAT including the melanocortin 4-receptor, mutations of which account for the largest genetic contribution to human obesity. This work also revealed heterogeneity in the SNS innervation of distinct WAT depots, underscoring for the field the importance of differential trafficking of autonomic activity across peripheral tissues, a research focus Tim’s laboratory continues to explore.
These neuroanatomical findings led to functional studies where Tim’s lab examined the physiological consequences of WAT sympathetic denervation via surgical nerve transection or local microinjection of neurotoxins that would selectively and locally destroy the sympathetic nerves. Remarkably, these interventions blocked lipolysis that normally occurs under conditions that promote lipid mobilization such as fasting, cold exposure, exercise and, in hamsters, photoperiod change. Collectively, his work on the SNS innervation of WAT has led to the now accepted conclusion that the sympathetic innervation of WAT is the principal initiator of lipolysis. This result prompted studies by multiple investigators yielding similar findings not only in laboratory rodents, but also in all mammals, including humans.
In the course of conducting the above research, Tim discovered an unappreciated and unanticipated role for the SNS innervation of WAT – the control of adipocyte proliferation. Adipocyte proliferation is the hallmark of obesity because without it, only a modest level of obesity would be achieved once existing adipocytes filled to capacity with lipid. The process of adipocyte proliferation and subsequent lipid filling is, however, not restricted and apparently can continue endlessly – thus the obesity problem. In conducting his WAT denervation studies, Tim found that sympathetic denervation, but not sensory denervation, triggers a profound adipocyte proliferation in vivo. The mechanisms underlying this effect remain unknown, but it is now well established that obese humans and rodents have decreased sympathetic drives to WAT, suggesting this may underlie the uncontrolled increase in fat cell numbers associated with this disease.
More recently Tim and his colleagues turned their attention to the intriguing question of whether WAT has a functional sensory innervation, and to identifying the nature of the signals arising from WAT that activate this innervation and are conveyed to the brain to influence SNS efferent control of adipose physiology and, more generally, energy balance. Using another viral tract tracer, the H129 strain of the herpes simplex virus-1, he discovered for the first time the sensory pathway by which WAT connects with and informs the central nervous system of events occurring in the fat pad. This H129 virus progresses in the anterograde direction (opposite to that of the PRV) and labels the sensory pathway connecting WAT to the brain involving a spinal sensory but not parasympathetic connection. Using electrophysiological recordings from the WAT sensory nerves, he and his collaborators (including Gary Schwartz and Johnny Garretson) are determining what is being sensed by these afferents, and it appears that these sensory nerves monitor some aspect of lipolysis. This information, in turn, could feedback to the brain to control lipid mobilization. Indeed, he and his lab members show that individual neurons in several brain areas that become infected when the sensory virus (H129) and sympathetic virus (PRV) are injected into the same fat pad highlighting the existence of a neuroanatomical complete SNS-spinal sensory feedback loops from WAT. This landmark work should prove critical to the understanding of the function and dysfunction of the central control of lipid mobilization so necessary for obesity reversal.
Complementary work on the neural control of BAT thermogenesis is found in one of Tim’s most recently published papers (Vitaly Ryu and colleagues) where his group tested whether individual neurons participate in SNS-spinal sensory crosstalk by injecting both PRV152 and H129 into intrascapular BAT (IBAT) of Siberian hamsters. They defined which spinal sensory neuron ganglion cells were activated using c-Fos immunoreactivity driven by β3-adrenoceptor agonist stimulation of SNS outflow to BAT (increasing BAT temperature; afferent nerve activity). Dually infected neurons were identified in multiple brain sites including raphe pallidus nucleus, nucleus of the solitary tract and hypothalamic paraventricular nucleus that are each strongly implicated in the control of BAT thermogenesis. These important results demonstrate SNS-spinal sensory feedback loops for BAT and suggest coordinated CNS control of BAT thermogenesis. Space limits a discussion of Tim’s important body of work of the neural and neuropeptide mediated control of foraging (food seeking) and food hoarding.
Tim’s PhD research with Robert Waldbillig and other work with Neil Rowland at University of Florida focused on the neural control of food and water intake involving analysis of serotonergic mechanisms and the use of diabetic models. He then trained as a postdoctoral fellow in three settings – at the University of Massachusetts with George Wade and with Bruce Goldman at the Worcester Foundation for Experimental Biology where he developed and pursued his work on photoperiod effects the obesity of Siberian hamsters and at University of Minnesota with John Morley and Allen Levine where he investigated effects diet, neuropeptides, cold exposure, and autonomic manipulations on feeding and metabolic efficiency. In 1988 he began a Assistant Professorship at Georgia State University where he remained becoming Professor in 1996 and Regents Professor in 2007. Tim’s work at Georgia State was funded by multiple NIH, NIMH, and NSF grants. A National Institutes of Health grant supported continuously for 27 years was recently funded for the 10 years via a NIDDK MERIT Award. His university also recognized the importance of his work and his nurturing of other faculty with obesity interests by establishing the Center for Obesity Reversal that has begun to flourish under Tim’s leadership.
Tim provided leadership to the field in many ways including multiple and continuous stints on NIH study sections, where he was a tireless advocate for the support of quality neural and neurobehavioral research on energy balance control, and an incessant voice for the inclusion of sufficient numbers of appropriate peer reviewers on otherwise diverse panels. He was a champion of early career investigators, advocating for inclusion of the professional development sessions at a variety of meetings. At Georgia State University, his long-term academic home, he taught a course he designed called “survival skills” to enhance the writing and presentation skills so important for graduate student success. He was active in three scientific societies: TOS (he was an original member of NAASO), the Society for the Study of Ingestive Behavior (SSIB), and the Society for Behavioral Neuroendocrinology. He was a dedicated member of TOS and served on its Annual Program Committee as chair of Track 2 and delivered a Keynote lecture at the Vancouver meeting to a huge crowd. At SSIB his served as its President, on its Board, and as an ardent advocate for annual giving.
Tim’s dedication to the future of his field and its science were manifest in the many ways he supported young investigators, as mentioned above, and in his mentoring of the graduate students, postdocs, and research scientists he trained. He nurtured his trainees by actively mentoring writing, presenting, and research skills and by the advocacy and loyalty he showed them as they sought, secured and advanced in their academic positions. Of the Masters , Ph.D , postdocs  and research scientists  he trained many occupy faculty positions throughout the US and abroad. Tim’s loyalty, generosity and sense of humor were among his most admirable qualities. He demonstrated these qualities continuously in his interactions with his son and daughter, his partner, former mentors, trainees, and colleagues at Georgia State, nationally, and around the world. His scientific colleagues were among his closest friends. The impact of Tim’s death is reverberating and will resonate among his numerous colleagues and many friends and trainees across the world. Tim lives on in his science and notably in the many personal relationships he forged in his work.
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Current Research Interests:
1) Control of lipid metabolism by the sympathetic nervous system and sensory innervation of white adipose tissue.
2) Control of thermogenesis by the sympathetic nervous system innervation of brown adipose tissue.
3) Environmental, neural and hormonal control of food acquisition (foraging and hoarding).
Obesity is a disease of figuratively and literally large proportions. Changes in body weight, reflected as changes in body fat, are realized through alterations in energy intake and /or energy expenditure. A wide range of animal species, including humans, can exhibit impressive seasonal increases and decreases in body weight and fat. We have been examining the naturally occurring changes in body weight and fat, as well as associated seasonal changes in reproduction, in several hamster species.
In these species we have found that the photoperiod (day-length) controls these and other seasonal responses. Siberian hamsters (Phodopus sungorus sungorus) decrease their body weight when exposed to short (winter-like) days; these decreases are reflected solely as decreases in body fat. We have demonstrated that the changes in the photoperiod are transduced into a neuroendocrine signal that triggers these seasonal responses based on the duration of secretion of the pineal gland hormone, melatonin. We have demonstrated the critical nature of the durational signal by giving daily programmed infusions of melatonin to freely moving, pinealectomized Siberian hamsters.
Funding is provided by National Institutes of Health (NIH) Grants/Fellowships:
National Institutes of Health MERIT Award R037 DK35254-26 to 36 “Photoperiodic Control of Obesity,” TJ Bartness (PI) 08/01/09-07/31/19, $3,000,200 (total direct costs)
National Institutes of Health Research Grant R01 DK078358-04 “Peptidergic Control of Appetitive Ingestive Behaviors”, TJ Bartness (PI) 03/15/07-03/14/11, $820,000 (total direct costs)
Sponsor: Ruth L. Kirschstein National Research Service Postdoctoral Fellow Award F32 DK082143 to Cheryl Vaughan (PI), “Interactions of sympathetic nervous and melanocortin systems in obesity reversal”, 06/01/09 – 05/31/12 $159,018 (total direct costs)
National Institutes of Health Research Grant R01 DK077975-01-05“Neuroendocrine Regulation of Adipocyte Metabolism”, MH Tschop (PI); subcontract TJ Bartness 01/15/09-12/31/13 $97,702 (total direct costs)